Master Theses UMCGhttp://scripties.umcg.eldoc.ub.rug.nl/
A repository of papers from college and university students who were investigating the MCG.
Work by students of the Faculty of Medicine of the University of Groningen and theses from other college and university students in the hospital, such as nursing, HLO, business, MER, Communication, Accounting and IT.
nl_NLNeonatal bloodspot screening for Medium-Chain Acyl-CoA dehydrogenase deficiency: evaluation of different screening parameters.
Background: Early diagnosis of Medium-Chain Acyl-Coenzyme A Dehydrogenase (MCAD) deficiency through neonatal bloodspot screening (NBS) and treatment significantly reduce morbidity and mortality. However, the NBS also detects false-positives (FP) as well as patients with ‘mild’ MCAD deficiency. In this study we investigated whether additional parameters could optimize the Dutch NBS, reduce FP and differentiate between severe and ‘mild’ MCAD deficiency.
Methods: A retrospective study of the NBS protocol detecting MCAD deficiency in the Dutch birth cohort between 2007-2015 was performed. The screening parameters C8, C6, C10, C10:1 and ratios C8/C10 and C8/C2 were evaluated in relation to genotypes and MCAD enzyme activity. In this study ‘mild’ MCAD deficiency was defined by ‘variant’ genotypes (genotypes that had not been identified in patients with clinical symptomatology) and/or high residual MCAD enzyme activity (≥10% measured in lymphocytes or leukocytes).
Results: 194 MCAD-deficient patients were identified in this study, of which 189 were detected through NBS. The prevalence of MCAD deficiency was 1/8,288 (95% CI: 1/7,265 – 1/9,645). The C8-cut-off showed a 99% sensitivity and approximately 100% specificity. The ratios C8/C10 and C8/C2 also correlated strongly with MCAD deficiency and combining the three parameters reduces the number of FP with 70%, at the expense of 22% of the ‘mild’ MCAD deficient patients. The C8/C10-ratio differentiated better than C8 and C8/C2 between severe and ‘mild’ MCAD deficiency.
Conclusion: This study confirms that the primary screening marker C8 is extremely effective to detect MCAD deficiency. Though, adding the ratios C8/C10 and C8/C2 would further improve the NBS protocol.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/KuijpersMM/
Mon, 22 May 17 07:28:51 +0200KIM-1 mediates the uptake of exosomes and transfer of MHC II
Urinary exosomes (EXO) are lipid membrane bound structures that mediate intercellular signaling through the transfer of proteins, miRNA and other factors. Kidney injury molecule 1 (KIM-1) acts as a phosphatidylserine (PS) receptor, inducing the uptake of apoptotic cells and necrotic debris. We hypothesize that KIM-1 acts as an endocytosis receptor, taking up EXO containing PS and mediating the intercellular exchange of signaling molecules, such as MHC II. LLC-PK1 cells expressing KIM-1 (PK1-KIM1) and cells expressing empty vector (PK1-pcDNA) were incubated with liposomes composed of PS and fluorescently labeled phosphatidylcholine (PC) or EXO isolated from LLC-PK1 cells, mouse dendritic cells (DC) or human urine by ultracentrifugation. EXO were fluorescently labeled with CytoTracker dye or MHC II-GFP. Uptake was quantified by measuring fluorescence intensity and flow cytometry. EXO were characterized by western blot and electron microscopy. MHC-II levels in urinary EXO from healthy subjects and CKD patients were determined by western blot. PK1-KIM-1 took up significantly more liposomes than PK1-pcDNA. EXO derived from LLC-PK1 cells, DCs and urine were positive for EXO markers HSP70, Flot-1 and TSG101. The diameter of EXO were between 30-150 nm. KIM-1 expressing cells took up significantly more EXO than empty vector expressing cells independent of the source of EXO. Urinary EXO from CKD patients were found to carry MHC II while EXO from healthy subjects were MHC II negative. We found the transfer of MHC II to primary PTCs to be greater in cells expressing KIM-1 after incubation with DC-derived EXO. We conclude that KIM-1 is a PTC receptor for EXO. MHC-II on EXO can be transferred to and presented by KIM-1 positive cells, suggesting EXO may serve to link dendritic cell activation to PTC MHC II expression and antigen presentation cells in inflammatory settings.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/KramersBJ/
Mon, 22 May 17 07:10:22 +0200Screening for prostate cancer - medical policy by general practitioners in the northern part of the Netherlands
Introduction - The prostate-specific antigen (PSA) test has been widely introduced in the nineties. The use of the test as a screening method for prostate cancer is highly debated worldwide. Advocates argue that the PSA test allows for early detection of prostate cancer and the resulting decline in mortality, while opponents state that the PSA test has more negative consequences such as overdiagnosis and overtreatment. Guidelines concerning screening differ per country, and GPs (general practitioner) within the same continent have distinctive methods of using the PSA test. The aim of this study was to characterize the medical policy of GPs in the northern part of the Netherlands regarding PSA screening for prostate cancer.
Methods - A questionnaire was developed by the German counterpart of the study. After translating the questionnaire, a pilot study was conducted to test for feasibility and validity. The renewed version was spread during a training day for GP trainees (n=23) and it was sent to 179 GPs in the catchment area of the University Medical Center Groningen (UMCG). The questionnaire was designed to determine the associations between medical policy regarding the PSA test and characteristics and attitude of the GPs and consisted of three topics. The first topic was the use of PSA testing in practice. The second topic concerned determinants of PSA testing strategies. The third topic concerned the use of guidelines in PSA testing strategies.
Results - The study had an average response rate of 36% (100%, and 27.9%, respectively; n = 73). Regarding the characteristics, GPs who worked in a duo or group practice were more likely to perform a PSA test if a patient actively requested it (p = 0.046). Working experience of ten or more years was associated with a smaller probability to recommend the PSA test to relatives (p = 0.047). Concerning the attitude, GPs that are afraid of missing prostate cancer and GPs who find screening for cancer in general unimportant are more likely to perform a PSA test when a patient asks for it (p = 0.017, and p = 0.043, respectively). The majority of the GPs discusses the benefits and disadvantages of the PSA test with patients who actively request screening for PSA screening. GPs who are not afraid of missing prostate cancer and who find screening for cancer in general unimportant are less likely to recommend the PSA test to relatives (p = 0.001, and p = 0.001, respectively).
Conclusion - Working in a duo or group practice and being afraid of missing prostate cancer are correlated with a higher probability to perform PSA testing when a patient actively asks for screening for prostate cancer. GPs with ten or more years of working experience and not being afraid of missing prostate cancer are less likely to recommend the PSA test to their relatives. Finding screening for cancer in general unimportant is associated with both being more likely to performing a PSA and not recommending the PSA test to relatives.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/KoopsL/
Wed, 12 Apr 17 12:49:11 +0200Popeye or Pinocchio? The relationship between muscle mass and grip strength in an elderly population by measuring muscle mass and testing grip strength
Background. The frailty syndrome is considered to be the most problematic expression of ageing. One of the underlying causes is a gradual decline in muscle mass and muscle strength. In the screening for patients at risk, standardization of the measurement instruments of loss of muscle is essential.
Objectives. This study aimed to measure muscle mass and muscle strength in elderly in order to correlate existing measurement instrument tools to each other. The second objective is to measure and correlate muscle density and muscle strength in elderly.
Design and setting. This prospective observational study included patients of 70 years and above visiting the outpatient clinic of the Gelre Hospital in Apeldoorn to undergo a Computed Tomography (CT) scan of the abdomen (January-April 2016). Muscle mass was calculated by Total Psoas Area (TPA). Muscle strength was measured by hand grip strength (GS). In pa-tients with identical amount of contrast fluid, muscle density was measured using the Houns-field Unit Average Calculation (HUAC).
Results. A total of 175 patients (median age 76 years) was included. After correction for con-founding factors (age, gender, and frail state) GS and TPA remained significantly correlated (R²=0.43, P=0.001). GS and HUAC were not significantly correlated (P=0.46 for men and P=0.39 for women). Influence of contrast fluid on HUAC was observed.
Conclusion. Although muscle strength (GS) and muscle mass (TPA) are correlated, they each symbolize different aspects of a patient’s physical condition. Muscle density (HUAC) is not correlated with muscle strength.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/KooijmanP/
Wed, 12 Apr 17 12:35:43 +0200The influence of posterior tilt of the femoral head on the failure rate of femoral neck fractures. Ananalysis of 164 undisplaced femoral neck fractures treated by Gannet osteosynthesis
Introduction: Failure rates of the so called undisplaced femoral neck fractures (FNF) vary from 4-23%. Literature states that undisplaced FNF always should be treated by internal fixation. The classification in undisplaced and displaced FNF is most commonly performed by the Garden classification. This classification is solely based upon the AP radiographs. Consequently the tilting of the femoral head in the anterior and posterior direction is not included in this classification. Over the years there have been many studies to identify pre- and post-operative predicators for failure. Yet posterior tilt, also known as retroversion or anterior angulation, of the femoral head as a predictor is only described by several authors. This study investigates two different methods to measure posterior tilt of the femoral head and its influence on the failure rate of undisplaced FNF.
Patients and methods: The posterior tilt of 164 undisplaced FNF treated by Gannet osteosynthesis were measured on the lateral X-ray of the hip using the Lateral Garden Angle (LGA) and the Posterior Tilt Measurement (PTM). Correlation between posterior tilt of the femoral head and the failure rate after Gannet osteosynthesis was assessed. Furthermore an intra- and inter observer reliability study was done with the two different methods to assess the validity of these measure methods.
Results: The overall failure rate was 5.5%. No correlation could be found between the posterior tilt of the femoral head and the failure rate if it was measured according to the LGA (P=0.366). If the posterior tilt was measured using the PTM a larger angle was associated with a higher failure rate (P=0.030). Retroversion of ≥20° measured using PTM is associated with a 4 times higher failure rate (OR = 4.286 (CI 95% 1.092 – 16.826) (P-value = 0.037)). The intra and inter observer reliability of the LGA was 0.765 and 0.601(P <0.001). For the PTM the intra and inter observer reliability was 0.790 and 0.773 (P <0.001).
Conclusion: The Lateral Garden Angle should not be used to measure posterior tilt because its validity is inferior to the Posterior Tilt Measurement. If the posterior tilt of the femoral head is measured using the PTM it is associated with a higher failure rate. Posterior tilt of ≥20° can be used as a significant predictor for failure in undisplaced FNF treated by Gannet osteosynthesis. The introduction of the PTM may lead to a paradigm shift in the operative treatment of the undisplaced FNF because it identifies that ‘stable’ FNF with a posterior tilt greater than 20° in fact behave like unstable fractures. Therefore the indication for internal fixation in the elderly patients will shift to a hip replacement if the posterior tilt of the femoral head rises above 20°.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/KalsbeekJH/
Wed, 12 Apr 17 12:23:00 +0200Combination therapy of antithrombin and alpha-1 proteinase inhibitor in a murine model of direct acute lung injury.
SUMMARY
INTRODUCTION
Acute respiratory distress syndrome (ARDS) is characterized by hypoxemic respiratory failure following an either direct (e.g. pneumonia) or indirect (e.g. sepsis) pulmonary insult. Dealing with hypoxemia remains the major challenge at bedside and is currently approached with lung-protective mechanical ventilation since specific treatment targeting the pathogenesis of ARDS is lacking.
Pathological hallmarks of ARDS are uncontrolled inflammation and coagulation leading to alveolar and interstitial edema, as well as infiltration of inflammatory cells in the alveolar space. Various cytokines, proteases and their inhibitors play a pivotal role in modulation of inflammation. Recent evidence suggests that proteinase inhibitors antithrombin (AT) and α1-protease-inhibitor (A1PI), may exert anti-inflammatory, anti-coagulant and immunomodulatory properties and may even have synergistic beneficial effect in diminishing inflammation. We hypothesize that combination therapy of AT and A1PI (COMBO therapy) has beneficial effect on lung damage and inflammatory markers in a murine model of direct acute lung injury.
METHODS
Balb/c mice (n=44) received 5 mg/kg LPS (E. Coli, 0127:B8) intranasally (i.n.) simulating direct acute lung injury (T=0). One hour later (T=1) the intervention drugs AT, A1PI only and COMBO therapy were administered intraperitoneally (i.p.) and at T=6 all mice were sacrificed. State of inflammation was determined using Luminex to quantify levels of inflammatory markers TNFα, IL-1β, IL-6, KC and IL-10 in plasma and bronchoalveolar fluid (BALF), and assessing total protein levels and neutrophil influx in BALF.
RESULTS
Intranasal LPS administration induced lung injury, evidenced by markedly increased levels of TNF-α and IL-1β in BALF and increased vascular permeability in all intervention groups and the control group compared to the vehicle group (P<0.05, for all groups compared to vehicle).
This study did not detect any differences with regards to markers of inflammation, neutrophil migration or alveolar-capillary permeability between the intervention groups compared to the control group.
CONCLUSION
This study investigated the combination therapy of AT and A1PI in a murine model of direct ARDS. No differences in markers of inflammation, neutrophil migration or alveolar-capillary permeability were detected between the intervention groups and the saline control group, not showing a beneficial effect of COMBO therapy. Future experiments are needed to test COMBO in different models, including pretreatment and an indirect lung injury model, to draw firm conclusions regarding the efficacy of COMBO.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/JuschtenJ/
Wed, 12 Apr 17 12:04:21 +0200Outcomes of the failure of selective nonoperative management of penetrating abdominal trauma
Introduction: Over the past five decades there has been a shift from mandatory operative
exploration to selective non-operative management (SNOM) in penetrating abdominal
trauma(PAT). Besides all the proven benefits of SNOM, the main concern is the potential
harm in patients who fail SNOM and eventually experience a delay in treatment. The aim of
this study is to investigate if delayed surgery due to failed SNOM is associated with adverse
effects in PAT patients.
Methods: All patients presenting at the Trauma Centre of Groote Schuur Hospital, Cape
Town in a 13-month period (05/15-06/16) were included. Patient groups were divided in
patients who went immediately for surgery and patients who failed SNOM and then had
surgery. Outcomes included mortality, morbidity rate and length of stay.
Results: Of 485 patients, 219 (45%) were managed by SNOM of which 26 (12 %) failed the
observation period and 266 (55%) with immediate surgery. The median time to OR was in the
immediate surgery group 5 hours (Q1-Q3 2-8) and in the failed SNOM group 45 hours (Q1-
Q3 27-68). Mortality was only observed in the immediate surgery group. There was no
difference in the number of patients who had complications (failed SNOM 31% vs. 37%
p=0.71), or in length of stay (failed SNOM median 7(5-10) vs. 7(5-12) p=0.95)
Conclusion: Under a structured clinical protocol, the delay does not cause preventable
mortality, morbidity or length of stay. Nevertheless further research has to be carried out to
emphasize our results.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/JoostenJJ/
Wed, 12 Apr 17 11:33:43 +0200The role of renal potassium excretion in serum potassium derangements in two different patient groups
Background
Potassium derangements are associated with increased mortality at the intensive care unit
(ICU). This study hypothesizes that increased renal loss of potassium plays a role in the
development of potassium derangements in patients with traumatic brain injury who received
thiopental to induce barbiturate coma (Study A) and in patients who were cooled to
therapeutic hypothermia (TH, 33°C) or therapeutic normothermia (TN, 36°C) following an
out-of-hospital cardiac arrest (OHCA) (Study B).
Methods
A single-centre retrospective study was performed. Serum potassium levels were used to
determine the incidence of potassium derangements. Potassium balances were calculated from
potassium intake and potassium excretion. In Study A three phases were compared; before,
during and after thiopental infusion. In Study B the hypothermia/normothermia phase
(HT/NT phase) consisted of two calendar days after admission. The post-HT/NT phase
consisted of two calendar days following cessation of the HT/NT phase.
Results
Five patients were included in Study A and 34 patients in Study B (n=16 for TH, n=18 for
TN). In Study A, the incidence of hypokalemia was higher during thiopental infusion
compared to before and after therapy, respectively, 100%, 60% and 25% (P=0.03). There
were no significant differences between potassium balances during thiopental therapy
compared to before and after therapy. In Study B, median cumulative potassium
administration during the HT/NT phase was 112 (IQR, 65 to 142) mmol in the TH group
compared to 36 (IQR, 25 to 54) mmol in the TN group (P<0.001), which resulted in median
serum potassium levels of, respectively, 4.2 (IQR, 3.9 to 4.6) mmol/L and 4.0 (IQR, 3.8 to
4.3) mmol/L (P<0.001). Hyperkalemia was more common in the TH group than in the TN
group, respectively, in 63% and 11% of patients (P=0.003). There was no difference in
median potassium balances between the TH group and the TN group (P=0.145).
Conclusion
In our study increased renal loss of potassium did not play an evident role in the development
of hypokalemia during thiopental infusion and during hypothermia. Since hypokalemia was
common during thiopental infusion whereas hyperkalemia was common during and after
cooling in the TH group, potassium should be monitored regularly in order to be able to adjust
potassium administration. An additional study with increased sample size is necessary to
determine the exact role of renal potassium loss in patients who received a barbiturate coma
or were cooled to hypothermia/normothermia after hospital admission with an OHCA.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/JongejanJ/
Wed, 12 Apr 17 11:26:34 +0200Erosieve gebitsslijtage, wat weten jongvolwassenen hierover en hoe wensen zij tandheelkundige informatie te ontvangen :Een multicenter studie onder jongvolwassen tandartsbezoekers in Noord-Nederland, binnen het project ‘Tandheelkundig Onderzoek en Prakt
Probleem- en doelstelling
Erosieve gebitsslijtage is een veel voorkomend verschijnsel onder de gehele Nederlandse bevolking. Bij jongvolwassenen zijn vaak al tekenen van deze slijtage te zien. Het is niet duidelijk of jongvolwassenen kennis hebben van erosieve gebitslijtage.
Dit onderzoek heeft als doel inzicht te verkrijgen in de mate van kennis over erosieve gebitsslijtage door jongvolwassenen. Tevens is beoogd inzicht te verkrijgen in de gewenste manier van het overbrengen van tandheelkundige informatie op jongvolwassenen.
Materiaal en methoden
Dit onderzoek is opgezet binnen het project van "Tandheelkundig Onderzoek en Praktijk Noord Nederland" (TOP-NN project). Aan het onderzoek hebben 25 praktijken deelgenomen. In het onderzoek zijn vragenlijsten ingevuld door jongvolwassen (20 t/m 25 jaar) tandartsbezoekers. In totaal zijn er 331 vragenlijsten geïncludeerd. De vragenlijst bevat vragen over een drietal onderdelen, namelijk de achtergrond van de deelnemer, de kennis omtrent erosieve gebitsslijtage en hoe de deelnemer tandheelkundige informatie wenst te ontvangen.
Op basis van de juiste antwoorden op de vragen naar de kennis over erosieve gebitsslijtage is een kennisscore opgesteld. De maximaal te behalen kennisscore was 24 punten.
De intraclass correlatie (ICC) voor de deelnemers in de mondzorgpraktijken was nul, dit houdt in dat de kennisscore erosieve gebitsslijtage van de jongvolwassenen onafhankelijk is van de mondzorgpraktijken waartoe zij behoren. Statistische toetsing is uitgevoerd met behulp van de Mann-Whitney U test, de Kruskal Wallis test en een lineaire regressie analyse.
Resultaten
De mediane kennisscore is 16 punten en de 25%-75% kennisscores zijn 13-18 punten. Vragen die vaak juist zijn beantwoord (88-97% juist) gingen over de erosieve aspecten van cola, energiedranken, vruchtensappen en sportdrank. Tevens zijn de niet-erosieve aspecten van water en mineraalwater (resp. 97% en 91% juist) ook bij veel jongvolwassenen bekend. De vragen die door minder dan de helft (9-44%) van de jongvolwassenen goed zijn beantwoord gaan over de gevolgen van erosieve gebitsslijtage, het effect van een droge mond, effect van water drinken direct na een zuurmoment, het niet-erosieve effect van yoghurt en het aantal eet- en drinkmomenten op een dag. Het aantal eet- en drinkmomenten op een dag is slechts door 9% van de deelnemers juist beantwoord.
De lineaire regressie analyse toont een significante mate van samenhang tussen de behaalde kennisscore en twee predictoren, namelijk een hoog opleidingsniveau en een deelnemer die eerder informatie over tandslijtage heeft ontvangen van zijn tandarts of mondhygiënist scoren hoger.
De meeste jongvolwassenen (67%) zoeken zelf niet naar tandheelkundige informatie. Als de jongvolwassenen wel willen zoeken naar tandheelkundige informatie dan geven zij de voorkeur aan dit te doen via een internetzoekmachine (80%) of door het te vragen aan de tandarts (56%).
De jongvolwassenen ontvangen het liefste tandheelkundige informatie door middel van een gesprek (81%), een folder (39%) of een e-mail (28%). Hierbij konden meerdere antwoorden worden aangekruist. De combinatie van een gesprek met een folder of e-mail is vaak gekozen.
Tevens geven de jongvolwassenen aan de informatie het beste te kunnen onthouden wanneer het hen wordt verteld (71%) of wanneer ze het kunnen lezen (51%). Ook hierbij konden meerdere antwoorden worden aangekruist. De combinatie van verteld worden en kunnen lezen veel gekozen.
Slechts 8% van de jongvolwassenen geeft aan tandheelkundige informatie te willen ontvangen door het aanraden van een app. Bij het zelf zoeken naar tandheelkundige informatie geeft 2% aan dit via de app van het Ivoren Kruis te doen en 3% geeft aan een andere app te gebruiken hiervoor.
Conclusie
De jongvolwassenen weten nog lang niet alles over erosieve gebitsslijtage. Het maximale aantal eet- en drinkmomenten is bij bijna niemand bekend. Hoog opgeleiden en jongvolwassenen die al eerder tandheelkundige informatie over erosieve gebitsslijtage hebben ontvangen hebben een significant hogere kennisscore.
De jongvolwassenen wensen te worden geïnformeerd door een gesprek met de mondzorgprofessional in combinatie met een folder of een e-mail. Het aanraden van een app is niet zinvol.
Voor het verhogen van de tandheelkundige kennis onder jongvolwassenen zal individuele mondelinge voorlichting ondersteund met schriftelijke informatie nodig zijn. Het ontwikkelen van effectieve individuele schriftelijke ondersteuning met extra aandacht voor de lager opgeleiden kan een volgende stap zijn tegen erosieve gebitsslijtage.
http://scripties.umcg.eldoc.ub.rug.nl/root/Tandheelkunde/2016/VerploegenVJN/
Tue, 11 Apr 17 14:27:02 +0200Het succes van endodontische behandelingen in een gedifferentieerde endodontologiepraktijk
Objectives
The aim of this study is to determine the success of endodontic treatment in a specialised en-dodontic practice and to identify factors predicting that success.
Method
In this study, the success rate of endodontically treated teeth was determined by looking at the healing and the survival of treated teeth. To achieve this, patient files were used in a retro-spective observation study. Using this method, a comparison was made between the preopera-tive status and the status at the time of recall, at least nine months after treatment. The surviv-al rate was decided by determining whether extraction took place or not. Healing was deter-mined by examining the clinical- and radiographic results. Assessment of these results were conducted using two criteria: strict- and loose-criteria.
Four factors were used for a significant predicting value on the outcome of healing: preoperative periapical radiolucency, complicating operative factors, the technical quality of the endodontic treatment, and the type of endodontic treatment. Statistical analysis was per-formed by using a logistic regression for outcomes of the several assessment criteria.
Results
Different study populations were performed by using the available information regarding rates of healing and survival. This research shows that 156 out of 157 teeth (99,4%) survived. By using the strict assessment criteria, 41 of the 131 teeth were classified as healed. Using the non-strict assessment criteria 109 of 131 teeth (83,2%) were classified as being healed.
The use of the strict criteria has shown a significant correlation between the presence or absence of a preoperative periapical radiolucency (OR: 95.55, p<0,001) and the presence or absence of complicating operative factors (OR: 5.91, p=0.029).
The use of the loose-criteria has shown a significant correlation between the presence or absence of a preoperative periapical radiolucency and the type of endodontic treatment (OR: 2.686, p=0.041).
Conclusions
Comments can be made within the limits of this study concerning the success of endodontic treatment in a specialised endodontic practice. This study shows that a preoperative periapical radiolucency in particular has a significant predicting value on the rate of healing. Further-more, complicating operative factors and the type of endodontic treatment that was used, show a significant predicting value, depending on the assessment criteria used.
Following the results of this study, additional research with multiple clinicians, work-ing at different endodontic practices is advised. Accessing the influence of specific elements of predictive values is advised. This would include the effect of the size of the preoperative periapical radiolucency and specific complicating operative factors.
http://scripties.umcg.eldoc.ub.rug.nl/root/Tandheelkunde/2016/ScheltesJP/
Tue, 11 Apr 17 14:09:36 +0200IMPLANT SUPPORTED SINGLE TOOTH REPLACEMENT IN THE AESTHETIC ZONE :A 10 year follow-up study of a prospective, randomized clinical trial comparing the treatment outcome of three augmentation modalities
OBJECTIVE: The aim of this randomized controlled trial was to assess the 10-year effects of three different augmentation techniques for implant supported restorations in the maxillary aesthetic region regarding clinical and radiographic parameters, and patient-centred outcomes.
MATERIAL AND METHODS: Ninety-three patients requesting single tooth replacement and presenting with a horizontal bone deficiency were included. After augmentation, 93 ITIEstheticPlus implants were placed. Clinical variables, standardised radiographs and
photographs and patient questionnaires were analysed to assess the impact of the various augmentation techniques 1 month (T1), 12 months (T12) and 120 months (T120) after final crown placement.
RESULTS: 10-years implant survival was 95.7% and did not differ between the groups neither were significant differences observed in the other treatment outcomes assessed. Peri-implant bone loss was low, viz. 0.48±1.19 mm (mesial) and 0.30±1.24 mm (distal) at T120. Loss of midbuccal marginal gingival level at T120 was 0.32±0.83 mm. Mean overall satisfaction at T120 was 8.6 with 98.6% of the patients satisfied.
CONCLUSION: Clinical, radiographic, aesthetic and patient centred outcomes were very
favourable after 10 years and did not differ between the groups with different bone
augmentation techniques.
http://scripties.umcg.eldoc.ub.rug.nl/root/Tandheelkunde/2016/meijndertC/
Mon, 10 Apr 17 13:50:32 +0200de conventioneel versus digitaal vervaardigde splint
Aim: The occlusal splint is an appliance used to influence the signs and symptoms of
temporomandibular dysfunction (TMD) and to protect the teeth from excessive wear due to
bruxism. There is no consensus in the literature about the therapeutic effect of occlusal splints,
however there is agreement on the behaviour changing effect. The explanation for this is that
because of the patients’ anticipation on the outcome of the intervention buxism decreases. This
underlines the importance of a well-fitting splint. The occlusal appliance can be manufactured
in a conventional way as by digital designing and thereafter milling the splint out of acrylic
resin. The aim of this study is to find out which method leads to a better result.
Materials and method: This study is a doubleblind randomised pilot study. The study
population was, after exclusion, a group of 34 dental students aged 20-35 years old. With these
students, alginate impressions of the upper and lower arch were made, as well as a wax bite in
maximal occlusion decreasing the vertical overbite with a minimum of 2,5 mm. One half of the
group received a conventionally manufactured splint without button anchors and the other half
received a digitally designed and milled splint. Both types of splint were of the Michigan type
with canine guidance. Research was done on the stone models, during the phase in which the
splints were placed and during a digital bite registration. The variables that have been measured
are occlusion, articulation, fit, retention and wear comfort. The programs R and IBM SPSS
were used to compare these variables in the study groups for statistical significance. In this
study a 95% confidence interval was chosen.
Results: A statistically significant difference between the two types of splint was found
in the variables fit ((U=84,000; p=0,036) and retention (p=0,001), both measured on the stone
models. In addition to that, a statistically significant difference was found in the retention
judged by the study population (p=0,01346) and the number of occlusal contact points in the
anterior region measured by the T-scan (U=78,000; p=0,020). All these mentioned differences
were in favor of the digitally designed splints. The variable occlusion in this study is subdivided
in ‘symmetrical contact between the left and the right side of the splint’, ‘the number of occlusal
contact points left and right on the splint’ and ‘simultaneous and evenly contact when coming
in occlusion’. The first two mentioned variables were measured with both articulating paper
and the T-scan and the last one mentioned was judged by the study population. Despite the fact
that no significant difference was found in the first two mentioned variables, the digitally
designed splints scored better on average than the conventionally manufactured splints which
shows a trend. This was also the case for the ‘wear comfort’ although both types of splint scored
low. This trend was not seen in the variables ‘articulation’ and ‘distribution of the bite force
measured by the T-scan’ and ‘simultaneous and evenly contact when coming in occlusion’.
Discussion and conclusion: The digitally designed and manufactured occlusal splint
scored, in most of the researched variables, better on average than the conventionally
manufactured splint. In a couple of cases this difference was also found to be statistically
significant. One can consequently say that there is a tendency in favour of the digitally
designing and manufacturing way of producing an occlusal splint.
http://scripties.umcg.eldoc.ub.rug.nl/root/Tandheelkunde/2016/KeurR/
Mon, 10 Apr 17 13:36:31 +0200Het gebruik van GC Fuji Triage® bij de behandeling van carieuze melkelementen
Summary
Background Most of the Dutch youth has dental caries or have had any experience
with it. There are several treatment options when the disease is no longer under control by the
patient. Most of those treatment seem very difficult because the child is in pain, is not yet
accustomed to visiting a dentist and the treatment of young children with extensive problems
is perceived as difficult by the dentist. There needs to be a treatment method that is quick and
easy to use but relieves the patients of the pain caused by dental caries. The treatment method
in which the lesion is covered with GC Fuji Triage® without giving local anaesthesia,
preparation or excavation in combination with giving instructions to the patient and regular
fluoride application could be a method that meets the objections inherent in the more invasive
treatment methods. However, it’s unclear whether the tooth can exfoliate without interference,
whether other treatment options can be explored when there is failure, whether this method is
applicable to both occlusal and approximal lesions and whether it is applicable to both
shallow and deep carious lesions.
Methods The study material was obtained from anonymous clinical records of children
with carious lesions covered with glass ionomer GC Fuji Triage® treated in referral practice
for Pediatric Dentistry in Ermelo. 140 patients enrolled in this study, a total of 690 carious
deciduous teeth were treated with GC Fuji Triage®. The following variables were measured
with each deciduous tooth: the survival (whether the coverage of the carious laesion
persevered until exfoliation), the location and depth (X-score) of the lesion and the total
duration that GC Fuji Triage® functioned as a hedge of the carious lesion. Finally, the raison
for failure was documented (minor or major failure). The data was analysed using IBM SPSS
Statistics 23.
Results Survival of deciduous teeth which are covered with GC Fuji Triage is
79,3%. 9,3% experienced minor failure, 11,4% major failure. The survival of occlusal lesions
(89,3%) is higher than the survival of approximal lesions (67,4%) and a higher survival rates
is seen at the lower X-ray scores (X-score 3: 83,5%, X-score 4: 61,5%, X-score 5 37,5%). In
premature failure of GC Fuji Triage® 9,3% of the deciduous teeth had a conventional
restoration or got a Hall-crown (minor failure). 11,4% of the deciduous teeth were extracted
(major failure).
Conclusion The treatment method of the disease caries in which a lesion is covered
with GC Fuji Triage® without without giving local anaesthesia, preparation or excavation in
combination with giving instructions to the patient and regular fluoride application seems to
be an alternative to the already existing treatment options of carious lesions in deciduous
teeth. The best results are seen with occlusal and shallow lesions.
http://scripties.umcg.eldoc.ub.rug.nl/root/Tandheelkunde/2016/GrootLGde/
Mon, 10 Apr 17 13:15:56 +0200The influence of ultrasonic scalers on the functioning of pacemakers and implantable cardio defibrillators; a systematic review
Objectives: The aim of the present study is to systematically evaluate the current
literature for the effect of ultrasonic devices, ultrasonic scalers in particularly, on
cardiac pacemakers and ICDs to add evidence based knowledge regarding health
risks of patients wearing these devices when treated with ultrasonic scalers.
Materials and methods: To conduct this systematic review the guidelines for the
Transparent Reporting of Systematic Reviews and Meta-analyses were used
(PRISMA statement). The National Library of Medicine, Washington DC (MEDLINEPubmed)
was selected in search of appropriate papers for this study. The search
was conducted starting from the earliest records until 04 May 2016. The structured
search strategy aimed at any published paper that evaluated the effect of ultrasonic
scalers on the functioning of pacemakers and/ or ICDs.
Results: The MEDLINE-Pubmed search resulted in 642 abstracts with one in
duplicate, a total of 641 abstracts remained. A total of 630 articles were excluded
after screening by title and abstract. The remaining 11 articles, consisting of in vivo
and in vitro studies, were selected for full text reading and all were eligible for the
purpose of this study. One additional paper was found eligible after reference
checking the list of the included studies. Considerable heterogeneity was observed in
the in vitro and in vivo studies. Therefore a quantitative analysis of the data was not
possible. A descriptive format was used to analyse the pooled data.
In five out of ten in vitro studies EMI (electromagnetic interference) with pacemaker
and/or ICDs was found when using ultrasonic dental scalers. This occurred when the
handle of the ultrasonic scaler was in close proximity towards the device in three of
those studies. In the remaining two studies interference at larger distances was
detected, but this was most probably because of interference with the telemetry
connection between pacemaker/ICD and the cardiac programmer device. None of
the in vivo studies demonstrated EMI in pacemakers and/or ICDs affecting the
functioning of these devices when using ultrasonic scalers. Interference with cardiac
programmers was also found to occur in vivo.
Conclusion: The findings of this literature study suggest that it is safe to use
ultrasonic scalers with patients who are fitted with a pacemaker and/or ICD. There is
no evidence these devices interfere with normal cardiac device function or damage
the device properties when interference takes place. When maintaining the
precaution distance of 10-15 cm. towards the cardiac device, no significant effect on
these devices is observed when using ultrasonic dental scalers.
http://scripties.umcg.eldoc.ub.rug.nl/root/Tandheelkunde/2016/DikME/
Tue, 04 Apr 17 08:57:18 +0200SPLIMP : Simultane botsplijting en implantaatplaatsing in de edentate bovenkaak ; Het evalueren van implantaten en prothetiek bij patiënten met een Cawoord IV of V geclassificeerde edentate bovenkaak na plaatsen van implantaten in combinatie met botsplijt
Objective: To evaluate the long-term outcomes of implant-supported maxillary overdenture, of simultaneous implant placement with the alveolar ridge expansion technique in the maxilla with insufficiency of alveolar ridges (SPLIMP) and the oral health –related quality of life (OHRQoL) of these patients.
Materials and methods: 22 patients of the Spaarne Gasthuis in Haarlem and Hoofddorp and the Red Cross Hospital in Beverwijk with insufficiency of alveolar ridges were treated using the SPLIMP technique participated in this study. The OHRQoL was determined by the patients at home. The clinical examination includes evaluation of implants osseo-integration, a X-ray was made to evaluate the bone loss comparing to the first taken X-ray taken after SPLIMP. Paired samples t-test was used to compare means. Also the effect of different bone augmentation materials and a resorbable membrane was evaluated using an ANOVA test.
Results: All implants were osseointegrated and no implant was lost. Regarding the bone loss, no significant differences were found between additional bone augmentation materials and without additional materials, Also no significant difference was found if a resorbable membrane was used.
Conclusions: Within the limitations of this study, SPLIMP has a high survival rate. The procedure seems to be save and predictable. Patients receiving implant-supported maxillary overdenture after SPLIMP have low scores on the OHIP-NL49.
http://scripties.umcg.eldoc.ub.rug.nl/root/Tandheelkunde/2016/BouwmanL/
Tue, 04 Apr 17 08:50:44 +0200De nauwkeurigheid van volumebepalingen van kaakbot bij het gebruik van Cone Beam Computed Tomography
Aim The aim of this research was to investigate the validity and reliability of volume measurements of bone with aid of the cone beam CT scanner. The influence of applied materials, like osteosynthesis screws and sutures, on the measurements was also investigated.
Methods A comparison is made between volume measurements on bone derived from a pig’s jaw created by the cone beam CT scanner and the golden standard. The golden standard consists of applying dental wax on the bone to avoid influx of water. The volume of the bone has been measured according to the water displacement method. A volume of water inside a beaker is compared to the watervolume after adding the bone and filling the beaker to the same level. With these measurements the bone volume can be calculated. 24 pieces of bone were used. On each piece 3 measurements were done, resulting in 72 measurements. To investigate the influence of applied materials, six bone augmentations were simulated. A CBCT scan was made after augmentation, a second CBCT scan was made after detaching the bone block from the augmentation site. The retreived volumes were compared.
Results Most of the volumes retrieved with aid of the CBCT differed significantly (α=0.05) from the measurements according to the golden standard. The measurements turn out the be very reliable. (Pearson correlatie test, r = .991, p = .000.) The influence of applied materials has not been verified in this investigation. (Wilcoxon-Signed Rank Test, z = -1.153, p = .249.)
Discussion The differences between volume measurements are mostly due to the ‘partial-volume’ effect, where voxels wich contain a little bit of bone will account for a completely filled voxel. Any trapped air bubbles during appliance of dental wax will result in a greater deviation of the retreived volumes. An analysis of grey values retreived from a CBCT scan is manually done, so the volume is also influenced by the analist. Conclusion It turns out that a volume measurement determined by the CBCT scanner is very reliable but not valid. The CBCT scanner with the used ‘threshold’ is not useful for determining exact bone volumes. Relative differences before and after bone augmentation can be measured with great reliability. The influence of applied materials like osteosynthesis-screws has not been verified.
http://scripties.umcg.eldoc.ub.rug.nl/root/Tandheelkunde/2016/BlomsmaI/
Tue, 04 Apr 17 08:27:23 +0200Behandeling van patiënten met ernstige kokhalsproblematiek :Een evaluerend onderzoek binnen het Centrum Bijzondere Tandheelkunde in het UMCG
Background: Gagging is a natural, protective reflex that occurs when a foreign object threats to come into the oropharynx. The gag reflex can be induced by different types of stimuli and the intensity differs for each individual. A disfunctional, extreme gag reflex can cause problems during the dental treatment or the wearing of a conventional denture. In the literature there is no agreement about the aetiology and prevalence from such a reflex. There is a lack of useful, valid measurement instruments and no consensus about the treatment method of preference.
Objective: The objective is to survey the patient population, treatment results and satisfaction among patients with gagging problemacy in a center for special dental care (CBT) in a hospital (UMCG) in Groningen, the Netherlands. Based on this, recommendations can be done to improve the treatment of patients with gagging problemacy.
Methods: It is an observational study that has been performed retrospectative. The patient list from the CBT in the UMCG was used. In the first part of the study, the patient dossiers from all patients that visited the CBT because of gagging problems from the 1st of January 2010 to the 1st of May 2016 were observed. This was followed by a structured interview with the patients who actually had been treated, provided that a VLEK (question list extreme gagging problemacy) was carried out during the intake. The structured interview contained several questions, including questions about the treatment effect on short-term and long-term, the satisfaction about treatment and positive/ negative elements of it.
Results: 116 patient dossiers were observed, of which 51 patients were selected for a structured interview. In 39 cases, a structured interview was actually performed. The majority of the referred patients consisted of male in the age of 40-60. More than half of the patients was referred by a general dental practioner. The self-reported short-term treatment effect was 4,95 on a scale from 0 (no effect) to 10 (gagging completely disappeared). The long-term effect differed not significantly (T = 94,50,
p= .180). The practioners recorded more often a positive effect for edentulous patients than for dentate patients, while not significant (U = 121, z= -2,027, p= .063). The mean rating for satisfaction about treatment was 7,95 on scale 0-10. Edentulous patiens were significant more satisfied than dentate patients (U = 97, z = -2,633,
p= .010).
Conclusions: Edentulous patiens are more satisfied about treatment for gagging problemacy at the center for special dental care in the UMCG than dentate patients.. This could be explained by the fact that the practioners recorded more often a positive effect for this group. Recommendations are improvement of the information provision (concerning treatment and treatment costs) and the administration with respect to appointments.
http://scripties.umcg.eldoc.ub.rug.nl/root/Tandheelkunde/2017/VriesJJde/
Tue, 04 Apr 17 07:22:46 +0200Een vergelijking van de effectiviteit van verschillende botsubstitutiematerialen ten behoeve van de opvulling van de alveole na extractie als voorbereiding op implantologische behandeling: een systematisch literatuur onderzoek
Purpose: the aim of this systematic review was to compare which bone substitution material has the best effectiveness in increasing the bone or reducing bone resorption after applying in the aveolus immediately after tooth extraction. The purpose of this comparison is to provide an up-to-date overview of the available scientific evidence of the effectiveness of various bone substitution materials for the purpose of alveolar ridge preservation.
Materials and methods: a systematic research is performed to identify and select articles who studied the effectiveness of several bone substitution materials for the purpose of alveolar ridge preservation. The data was compared with the aid of a descriptive analysis, which subdivided the data by measuring method and mean follow-up.
Results: of the 351 identified articles, 18 were included in this systematic review. In the included articles, different bone substitution materials were compared to other bone substitution materials or to control groups where no bone substitution materials were used. The comparison of clinical data revealed that Bio-Oss® has the best effectiveness after 12 weeks to 3 months, that Bio-Oss® + BPAM, CaS + DFDBA and Bio-Oss® + BioGide® have the best effectiveness after 16 weeks to 4 months and that NanoBone® + BioGide® and Bio-Oss® + BioGide® have the best effectiveness after 6 to 7 months. The comparison of radiographic data revealed that Bio-Oss® has the best effectiveness in increasing the radiographic bone density after 12 to 14 weeks and that MGCSH + ConFORM® and CRP + ConFORM® have the best effectiveness in reducing the loss of vertical bone thickness after 3 months. The comparison of histological/histomorphometric data revealed that CRP + ConFORM® have the best effectiveness in increasing the mean percentage of new/vital bone after 12 weeks to 3 months, that MEHA has the best effectiveness in increasing the mean percentage new/vital bone after 16 weeks to 4 months and that NHA + CS and BHA + CS have the best effectiveness in increasing the mean percentage of new/vital bone after 5 to 7 months.
Conclusion: the choice of bone substitution material that has the best effectiveness for alveolar ridge preservation depends on the measuring method and on the time of measuring. It can be concluded that the best time to place dental implants is 4 months after extraction and ridge preservation using Bio-Oss® + BPAM if the aim is the preservation of de clinical horizontal bone thickness. If preservation of the vertical bone thickness is the aim, the best time to place dental implants is 19 weeks after tooth extraction and alveolar ridge preservation with 70% FDBA + 30% DFDBA with d-PTFE membrane.
http://scripties.umcg.eldoc.ub.rug.nl/root/Tandheelkunde/2017/RulerBvan/
Mon, 03 Apr 17 13:11:04 +0200Early feeding habits in relation to oral health in children – a systematic review
Background Type of feeding during the first period of a child’s life can play an important role in the development of their oral health. The aim of this review was to give an update of available literature on the influence of breast- and bottle-feeding on the development of caries, erosion and the occlusion in children.
Methods PubMed was searched for relevant studies published until December 2016. All studies including data on breastfeeding and/or bottle-feeding and their influence on the development of caries, erosion and the occlusion, were included. Two independent reviewers assessed the studies’ eligibility and quality, and extracted data from the included studies. Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomized Studies in Meta-Analyses was used for quality assessment.
Results At the end of the screening process, 30 studies remained for inclusion: 20 considering caries, 1 considering erosion, and 9 considering occlusion in relation to breast- and bottle-feeding. Breastfeeding was found to have a protective effect on development of caries, but early weaning (<3 months) and prolonged breastfeeding (>24 months) were associated with higher caries experience. In addition, bottle-feeding was found to be associated with higher caries experience. Children who were weaned at an early age (<12 months) were more affected by erosion than those weaned at a later age. Breastfeeding was found to lead to normal occlusion more often than bottle-feeding. Occlusal parameters more commonly found in bottle-fed children included terminal planes that do not favour correct occlusion, unfavourable intercanine and intermolar diameters, posterior cross bite development and open bite. The quality scores of included studies showed high variety.
Conclusion Results indicate that breastfeeding has a protective effect on caries experience, reduces the risk of developing erosion and more often leads to normal occlusion compared to bottle-feeding. Further research is recommended to strengthen the evidence.
http://scripties.umcg.eldoc.ub.rug.nl/root/Tandheelkunde/2017/PetersAJF/
Mon, 03 Apr 17 12:51:02 +0200Morfologisch contourherstel bij directe klasse II composiet restauraties bij het gebruik van verschillende Sectionele Matrixsystemen
Doelstelling: In deze studie is onderzoek gedaan naar 3 verschillende sectionele matrixsystemen op contour- en contactpuntherstel bij klasse II restauraties.
Materiaal en methode: Er zijn in dit onderzoek 3 matrix-systemen getest: het Contact-matrixsysteem, V3-matrixsysteem en het Twinring-matrixsysteem. Met behulp van een kolomboor zijn in 60 KaVo-elementen identieke preparaties gemaakt die in 3 groepen zijn ingedeeld. Per onderzoeksgroep zijn 20 elementen geïncludeerd die at random zijn verdeeld. Groep 1: 20 KaVo elementen gerestaureerd met behulp van het contact-matrixsysteem. Groep 2: 20 KaVo elementen gerestaureerd met behulp van het V3-matrixsysteem. Groep 3: 20 KaVo elementen gerestaureerd met behulp van het Twinring-matrixsysteem. Deze elementen zijn beoordeeld op occluso-gingivale en bucco-linguale contour vanaf buccaal gezien en vanaf occlusaal gezien en vergeleken met een oorspronkelijk, niet-gerestaureerd KaVo-element. Met behulp van een opstelling zijn vanaf een exact identieke positie foto’s gemaakt van de elementen. De foto’s zijn geanalyseerd met behulp van Matlab en meetbaar gemaakt. Tevens is er met een flosdraad gekeken of er een contactpunt is en is er beoordeeld of er sprake is van een contactpunt of een contactvlak.
Resultaten: De gemiddelde bucco-linguale afwijking(uitgedrukt in pixels) met het oorspronkelijke element met hun standaarddeviaties zijn: groep 1(-20,54 ± -6,08) > groep 2(-16,44 ± 4,55) > groep 3(-13,61 ± 4,92). Wat betreft de occluso-gingivale contour zijn de resultaten: groep 1(-19,02 ± 6,06) > groep 3(-14,15 ± 3,11) > groep 2(-13,51 ± 3,26). Het verschil tussen groep 1 in vergelijking met groep 2 en 3 is significant, maar het verschil tussen groep 2 en 3 is niet significant.
De gemiddelde maximale bucco-linguale afwijking in vergelijking met het oorspronkelijke element is: groep 1(-32,85 ± 6,92) > groep 2(-28,10 ± 6,67) > groep 3(-24,15 ± 5,23). Die van de occluso-gingivale contour zijn: groep 1(-35,6±7,34) > groep 2(-32,35 ± 4,99) > groep 3(-30,50 ± 3,47). Hierbij is het verschil tussen groep 1 en 3 wel significant maar de andere verschillen niet.
Bij alle restauraties is een contact gecreëerd met het buurelement. Bij de meeste restauraties is een contactvlak gevormd(61,67%) bij de overige elementen is een contactpunt gecreëerd(38,33%). In groep 1 komt het vaakst een contactvlak voor(85%). Bij de andere 2 groepen is dit respectievelijk 45% en 55%.
Conclusie: Bij gebruik van alle drie sectionele matrixsystemen wordt contact gecreëerd met het buurelement. Restauraties met behulp van het V3-matrixsysteem en het Twinring-matrixsysteem zorgen voor een beter contour herstel dan bij het gebruik van het contact-matrixsysteem. Echter zorgt deze laatste voor strakkere contactpunten.
Trefwoorden: Sectionele matrixsystemen, Twinring-matrixsysteem, V3-matrixsysteem, contact-matrixsysteem, contour, contactpunt.
http://scripties.umcg.eldoc.ub.rug.nl/root/Tandheelkunde/2017/KeulenGB/
Mon, 03 Apr 17 12:45:22 +0200Tandartsbezoek en de oudere patiënt
People are getting older. Healthy aging and longer living at home is the objective in healthcare and politics. This study looked at the rapidly growing group of independently living elderly people and the factors that affect their dental visit. A questionnaire was sent to 308 patients in a general practice. The response rate was 53%. The study population was satisfied with the accessibility of the dental practice. The majority of the study population regularly came for inspection at the dentist. Impeding factors were mainly patient associated, namely: motivation, complaint motivated dental visit, planning and making of appointments, dentate status, having an additional insurance and whether to respond to a recall. Patients with additional dental insurance visited the dentist significantly more frequent. With an active recall policy, the attendance rate is likely to be increased.
http://scripties.umcg.eldoc.ub.rug.nl/root/Tandheelkunde/2017/EbbensOEJ/
Mon, 03 Apr 17 12:19:42 +0200The impact of different nCRT schedules on localization of tumor recurrences in esophageal cancer patients
Background: Identification of a different distribution and pattern of recurrent disease in
esophageal cancer (EC) patients is important for a better understanding of tumor biology and the
effect of neoadjuvant chemoradiotherapy (nCRT). This study assessed the influence of two
different nCRT regimens (cisplatin/5-fluorouracil with 50.4 Gy (Cis/5FU) versus
carboplatin/paclitaxel with 41.4 Gy (CROSS)), on the distribution of recurrent disease and distant
metastases in EC patients.
Patient and Methods: In this retrospective study, locally advanced EC patients (stage II/III)
treated between 2002 and 2015 with nCRT followed by a curative intended esophagectomy (open
transthoracic or scopic procedure), were included. The CROSS patients were all treated in the
University Medical Center Groningen in The Netherlands and the Cis/5FU patients were treated
in the Flinders Medical Centre in Australia. We assessed the difference in site-specific tumor
recurrence. We also assessed the 5-year overall survival (OS) and 5-year disease-free survival
(DFS) with univariate and multivariate Cox regression analysis.
Results: One hundred and thirty-eight (n=138) EC patients were included in analysis. The
amount of distant metastases (P=0.039), lung metastases (P=0.017), and peritoneal metastases
(P=0.039) differed significantly between the groups. The treatment schedule was not a
prognostic factor in multivariate Cox regression analysis for both 5-year DFS (P=0.232) and 5-
year OS (P=0.602).
Conclusion: The CROSS and Cis/5FU group differed significantly in the total amount of
recurrences, with more tumor recurrences in the CROSS group. However, the 5-year OS and DFS
did not differ.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/jippingKM/
Tue, 28 Mar 17 12:27:06 +0200Development of Participation Scale addressing participation restrictions in children who suffered from Buruli Ulcer in Benin and Ghana
Introduction: Buruli Ulcer (BU) is a debilitating skin disease caused by Mycobacterium ulcerans and when left untreated often results in scarring and retraction of the area and can lead to permanent disability.
Objectives: To develop an adequate questionnaire assessing possible participation restrictions in former BU patients younger than 15 years old in Benin and Ghana.
Methods: The research is divided into phases. Phase I consists of item collection by means interviews and observation, item selection and item reduction corresponding with the International Classification of Functioning, Disability and Health ICF domains. Phase II consists of a pilot study aiming to test the comprehensibility, feasibility, relevance and acceptability of the draft questionnaire 58 participants in Benin. Phase III consists of testing content validity, reactivity and discrimination of the new developed scale by means of appropriate statistical methods among 109 participants in Ghana.
Results: In Phase I a draft questionnaire was developed with 25 questions. Testing in Phase II resulted in the elimination of 16 of the 25 questions. The 7 questions, with an internal consistency, Cronbach's alpha of .539 were used for further testing Phase III. 73 (63%) participants score 0 on the Participation Scale. The mean of participants scoring > 0 is 7.772 and the median 5.00 with highest possible total score on the P-scale being 35. Gender is an independent factor, with females having higher outcomes.
Conclusion: A measure is developed to determine participation restrictions in former BU below 15 years. It is the first time to establish that this group of patients face participation restrictions. Further research is required to determine cut-off score, enhancing the questionnaire validity and reliability. Moreover research is to determine the adequate methods and programmes to reduce participation restrictions in this patient group.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/HorstmanJ/
Mon, 27 Mar 17 09:23:39 +0200De werkenemer als boormachine? : Stage wetenschap ethiek, bedrijfsgeneeskunde en Quantified Self
This is a qualitative research on the responsibilities for health and health promotion in the workplace, from the perspective of new technologies like wearables and Quantified Self. This research is divided into two parts; the first part being a literature study, the second part consists of interviews with occupational physicians (OP’s). 7 OP’s were interviewed, and these interviews were coded and analyzed with use of ATLAS.ti.
Both the literature study and the interviews show that it is not possible to hold one party responsible for health in the workplace. The employee can be held responsible for his own health to a great extent. Nevertheless, bad health can also be a result of socioeconomic status, bad luck or lack of rational action, and the individual cannot be held accountable for those factors. A number of OP’s explained this individual responsibility of the employee with comparing them to a machine. This machine metaphor can be traced back to the 18th century tradition of materialism in medicine.
Another part of the responsibility for health in the workplace lies with the employer. He could be held responsible for creating an healthy workplace and facilitate the options for the employee to make the right health choices. The OP’s could be responsible for guiding both parties, and giving them the right medical information and background. This task will be increasingly important with the rise of new technological interventions and eHealth. Through activity trackers like pedometers this type of eHealth can be applied in the workplace. Activity trackers are a rapidly developing branch of corporate wellness, which has yet to gain evidence of its health effect. These technological applications are intertwined with our everyday lives and can have an effect on health behavior with merely being there – both in the workplace and beyond. OP’s stated that they were interested in using these technologies in their daily practice, as long as there is enough evidence for their health effect. The question is whether these developments fit in the tradition of evidence based medicine, because they are integrated with many more aspects of daily life. That is why these developments require a more culture-analytic and interdisciplinary approach.
As a result of the above mentioned technologies and pressure from the government to keep costs of healthcare as low as possible, there is a shift towards preventive medicine. This research shows that if the OP’s want to keep on track with these developments, their profile might be in need of a reassessment. There is a need for a holistic view on health in the workplace, with an emphasis on continuity of healthcare, integration of new technologies and cooperation with doctors from the curative field of healthcare.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/HoogenRFMvanden/
Mon, 27 Mar 17 09:10:10 +0200Influence of deep brain stimulation of the subthalamic nucleus on cognitivesymptoms in a rat model of Parkinson’s Disease
Morbus Parkinson is a common neurodegenerative disease. It is best known for its cardinal
motor symptoms caused by loss of dopamine, which can be alleviated by dopaminergic
medication and deep brain stimulation (DBS) of the subthalamic nucleus (STN). But most
patients also have non-motor symptoms. Attention deficit and impulsivity are among the
commonest. There are indications that STN DBS affects these cognitive symptoms.
Nevertheless, there is a lack of properly controlled studies, not confounded by varying
influences. Therefor a study was performed to test attention and impulsivity in a rat model of
parkinson’s, as well as the effect of STN DBS, thereof.
A 3-class auditory oddball paradigm was used to test rats’ ability to quickly, and specifically
react to a correct tone, but to ignore a standard and distractor tone. Our results show reduced
attention and impulsivity in the 6-OHDA lesioned rat Parkinson’s model, but that STN DBS
has no effect on these symptoms. Reduced attention has been shown in Parkinson before,
while the impact of this disorder on impulsivity is less clear. This paradigm may therefore be
useful to characterize the pathophysiological mechanisms leading to disturbed attention in
Parkinson in more detail.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/HolslagJAH/
Mon, 27 Mar 17 08:50:43 +0200Vragen naar het vraaggedrag van patiënten: een kwalitatief onderzoek naar de ervaringen van patiënten en de rol van sociale verwachtingen bij het stellen van vragen tijdens een medisch consult
Vanuit de maatschappij wordt van patiënten verwacht dat ze zelf verantwoordelijkheid nemen voor hun eigen gezondheid en zorg (Raad voor Volksgezondheid en Zorg, 2012; Rijksinstituut voor Volksgezondheid en Milieu, 2014). Om eigen regie te voeren is het nodig om actief op te treden en mondig te zijn in de gezondheidzorg. Toch is het niet vanzelfsprekend dat iedere patiënt in staat is om mondig te zijn en vragen stelt aan een arts. In opdracht van het Universitair Medisch Centrum Groningen is dit onderzoek uitgevoerd met als doel inzicht te krijgen in de ervaringen van patiënten bij het stellen van vragen aan een arts tijdens een medisch consult. Daarbij is onderzocht in hoeverre verwachtingen vanuit de sociale omgeving, de maatschappij en vanuit artsen invloed hebben op het stellen van vragen door patiënten tijdens een medisch consult.
De Theory of Planned Behavior is gebruikt om te achterhalen wat het vraaggedrag van patiënten kan verklaren. Uit de literatuur komt naar voren dat er vrijwel niets bekend is over patiëntervaringen waar sociale verwachtingen een invloed spelen rondom het vraaggedrag van patiënten. Om die reden is explorerend onderzoek uitgevoerd aan de hand van de kwalitatieve onderzoeksbenadering van Hennink, Hutter en Bailey (2011). Interviews zijn gehouden met tien patiënten die voor een eerste consult op de afdeling Orthopedie kwamen. Met behulp van een interviewschema zijn de patiënten geïnterviewd. Deze interviews zijn vervolgens geanalyseerd met het programma ATLAS.ti
Sommige patiënten voelden zich niet gehinderd bij het stellen van vragen, maar bij sommigen leek dat wel het geval. Dat waren met name oudere patiënten, wat te maken kan hebben met het vroegere heersende idee ‘doctor knows best’ waarbij het niet gebruikelijk was om vragen te stellen aan de arts. De voorbereiding lijkt van belang te zijn voor het vraaggedrag van patiënten. De ene patiënt bereidt vragen voor en de ander doet dit niet. Dit heeft te maken met de hoeveelheid ervaring patiënten hebben opgedaan met arts-patiënt gesprekken, met eerdere klachten en door het praten met andere mensen, maar ook met het vertrouwen in de arts en het karakter van de patiënt. Toch hoeft de manier van voorbereiding niet altijd uit te maken, want ook opspelende emoties van de patiënt en de informatieverstrekking van de arts lijken het vraaggedrag van patiënten altijd te kunnen beïnvloeden.
Sociale verwachtingen lijken in meer en mindere mate het vraaggedrag van patiënten te beïnvloeden. De mate van invloed door de directe sociale omgeving, de maatschappij en vanuit artsen op het vraaggedrag van patiënten verschilt. Zo blijkt dat de directe sociale omgeving invloed kan uitoefenen op patiënten bij het bedenken en stellen van vragen tijdens een medisch consult. Patiënten vergaren informatie door met anderen binnen het sociale netwerk te praten en gebruiken deze informatie als input voor de vragen die ze bedenken om de arts te stellen. Enkele geïnterviewde patiënten stellen vragen, omdat dit van personen uit hun directe sociale omgeving moet. Minder duidelijk is de invloed vanuit de maatschappij en vanuit artsen op het vraaggedrag. Sommige patiënten gebruiken het internet als informatiebron voor het bedenken van vragen. Daarnaast lijken de geïnterviewde patiënten tegenwoordig anders aan te kijken tegen het stellen van vragen aan een arts dan dat zij vroeger deden. Patiënten lijken te weten dat de arts van hen verwacht dat ze alle informatie moeten geven aan de arts en de arts vragen moet stellen als ze informatie niet begrijpen. Geen van de geïnterviewde patiënten stelt vragen, omdat zij het idee hebben dat de maatschappij, de overheid of artsen dit van hen verwachten. Als patiënten vragen willen stellen, stellen ze deze omdat ze dit over het algemeen zelf willen en laten ze zich niet beïnvloeden door sociale verwachtingen.
http://scripties.umcg.eldoc.ub.rug.nl/root/anderestudie/2017/StokkersL/
Wed, 15 Mar 17 10:24:23 +0100EXPLORATIEF ONDERZOEK NAAR DE MOGELIJK MODERERENDE BIJDRAGEN VAN DOPAMINERGE EN SEROTONERGE POLYMORFISMEN AAN HET EFFECT VAN NASAAL TOEGEDIENDE OXYTOCINE OP DE SOCIALE ORIËNTATIE RESPONSES BIJ JONGE MANNEN MET EEN AUTISME SPECTRUM STOORNIS
Doel: In dit onderzoek werd gekeken naar de invloeden van enkele dopaminerge en serotonerge polymorfismen op de elektrofysiologische responses op empathie oproepende afbeeldingen en hun invloed op de effecten van intranasaal toegediende oxytocine op deze responses bij normaal intelligente volwassen mannen met en zonder een autisme spectrum stoornis (ASS).
Methode: Het betreft een gerandomiseerde dubbelblind placebogecontroleerd crossover onderzoek bij gezonde mannen en mannen met ASS. Om te beginnen moesten de deelnemers een aantal vragenlijsten invullen. Uit het bloed zijn de dopaminerge en serotonerge polymorfismen (DAT1, DRD2, DRD4, DRD5, COMT, DBH, MAO-A en 5HTTLPR) bepaald. Vervolgens kreeg de onderzoekspopulatie een placebo of oxytocine (OXT) toegediend voordat ze empathie oproepende afbeeldingen kregen te zien. De afbeeldingen zijn afkomstig van het “International Affective Picture system”(IAPs). Hierbij kregen de deelnemers afbeeldingen te zien met evenveel plezierige als onaangename en neutrale afbeeldingen met en zonder mensen. Terwijl de afbeeldingen werden bekeken, werd er met behulp van een EEG de event-gerelateerde Long Latency Parietal Positivity (LPP) gemeten.
Resultaten: De dragers van het A1-allel van het DRD2-gen lijken een geringer sociale oriëntatie respons te hebben. Dit geldt ook voor de homozygote dragers van het 4-repeat allel van het DRD4-gen en de dragers van het A1-allel van het DBH-gen. Verder lijken in de controlegroep de homozygote dragers van het 3-repeat allel van het MAO-A-gen een groter elektrofysiologische respons te hebben op de aversieve afbeeldingen. Dit geldt ook voor de dragers van het S-allel van het 5-HTTLPR-gen in de controlegroep. Daarnaast leek bij de dragers van het A1-allel van het DRD2-gen de ASS-groep meer baat te hebben bij het toedienen van OXT dan de controlegroep. Dit geldt ook voor de homozygote dragers van het 4-repeat allel in de ASS-groep van het MAO-A-gen. De homozygote dragers van het La-allel van het 5-HTTLPR-gen leken in de ASS-groep ook meer baat te hebben bij OXT toediening dan de homozygote dragers van het S-allel. Er lijkt dus sprake te zijn van een aan de klinische status differentieel gerelateerde respons.
Conclusie: De polymorfismen van het DRD2-, DRD4-, DBH-, MAO-A- en het 5-HTTLPR lijken dus invloed te hebben op de sociale oriëntatie respons op empathie oproepende afbeeldingen. Daarnaast lijkt de klinische status invloed te hebben op de manier waarop de verschillende polymorfismen het effect van OXT op de LPP-respons modereren (DRD2, MAO-A en 5-HTTLPR).
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/HoebasSO/
Wed, 15 Mar 17 10:15:31 +0100Pulmonary involvement in primary Sjögren’s syndrome
Background: In previous studies in primary Sjögren’s syndrome (pSS), the prevalence of
pulmonary involvement varied greatly depending on differences in inclusion criteria and
definitions of pulmonary involvement. The ESSDAI has been developed for standardized
assessment of the main organ involvements. Our aim was to evaluate the prevalence and types
of pulmonary involvement in pSS patients and to classify the manifestations using the
pulmonary domain of the ESSDAI.
Methods: This retrospective cohort study included all consecutive pSS patients, fulfilling the
AECG and/or ACR classification criteria, who visited the department of Rheumatology and
Clinical Immunology of the UMCG in 2015. Data were obtained from electronic patient records
of the first visit in 2015. In some cases, the difference between pulmonary manifestations
caused by pSS or coincidental factors remained unclear, resulting in a range of assumed to
possible pulmonary involvement in pSS.
Results: Of the 262 included pSS patients, 93% were female and mean age was 56 ± 15 years.
Pulmonary complaints were present in 88 (34%) patients. Additional pulmonary diagnostics
was performed in 225 (86%) patients. Pulmonary involvement was present in 25-39 (10-15%)
pSS patients. Overall, most common was interstitial lung disease (ILD), which was present in
15 patients; especially non-specific interstitial pneumonia (NSIP). In total, 16 (6%) patients had
a positive ESSDAI for the pulmonary domain; low activity (n=4), moderate activity (n=11) and
high activity (n=1).
Conclusion: In this cross-sectional study in daily clinical practice, pulmonary involvement was
present in 10-15% of pSS patients, most common ILD. Of all pSS patients, 6% were scored as
active on the pulmonary domain of the ESSDAI.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/HeusA/
Wed, 15 Mar 17 10:11:06 +0100Protective Effects of Pharmacological TPRM2 Inhibition on Ischemia-reperfusion Injury of the liver
IBsachckemgrioa-urnepde rfusion injury (IRI) of the liver is a common clinical problem after liver surgery
and transplantation and new therapies are required to prevent it. Calcium overload in
hepatocytes plays a central role in the pathogenesis of IRI, but the nature of the Ca+ channels
responsible for this is unknown. Accumulating evidence shows that the Transient Receptor
Potential Melastatin 2 (TRPM2) channel, which is activated in oxidative stress, could play a
major role in Ca2+ overload. This study aims to investigate whether pharmacological inhibition
of TRPM2 could reduce IRI of the liver in rats and mice.
TMweoth doidffse rent types of experiments were conducted. In the first experiment, rats were subjected
to 45 minutes of liver ischemia and 1 hour reperfusion. Each animal randomly received one of
the TRPM2 inhibitors - chlorpromazine (n = 3), N-(p-amylcinnamoyl)anthranilic acid (ACA)
(n = 3) or curcumin (n = 4). The control groups only received the vehicles (n = 3) prior to
ischemia. Bile flow recovery during reperfusion was used to assess final liver damage.
In the second experiment, mice were subjected to 45 minutes of liver ischemia and 24 hours of
reperfusion. Each mouse randomly received either TRPM2 inhibitor curcumin (n = 8) or its
vehicle (n = 7) prior to ischemia and at the start of reperfusion. TRPM2-KO mice were used
as positive control group (n = 4). ALT and AST levels and liver histology after reperfusion
were used to assess final liver damage.
IRne tshuel tesx periments using rats, no significant difference in bile flow recovery was found between
ACA and its vehicle, and between curcumin and its vehicle. Rats treated with chlorpromazine
showed significantly less bile flow recovery compared to the vehicle treated group.
In the experiments using mice, ischemia increased AST and ALT enzyme levels compared to
sham-operated controls. No significant differences in ALT and AST levels were found between
mice treated with curcumin and mice treated with its vehicle only. Interestingly, enzyme levels
in TRPM2-KO mice were not significantly lower compared to levels in WT mice. Comparing
percentages of necrosis, similar results were found between these groups.
TChoenscel udsaitoan d o not show a reduction in liver IRI through pharmacological TRPM2 inhibition.
Further research on the role of TRPM2 channels in liver IRI is needed.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/HaasJde/
Tue, 14 Mar 17 12:57:39 +0100Connective Fields (CF) in de vroege visuele cortex bij patienten met een psychotische aandoening
abstract not avalable
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/GrootJebbinkW/
Tue, 14 Mar 17 11:49:41 +0100The concept of micro-merging within professional services: a case study in the dutch healthcare industry
Although the literature on mergers and acquisitions (M&As) is quite advanced, analyses of micro-mergers—mergers of internal functional units within the same organization—remain limited. Clarification is needed regarding micro-mergers and their effects on performance. Therefore, this case study investigated micro-mergers within professional service firms (PSFs), specifically focusing on healthcare providers. Thereby, this study addresses the following research question: How do different types of micro-mergers affect the performance of PSFs?
Thus, it examined the various types of micro-mergers and the relationship between the type of micro-merger and PSF performance. In addition, it focused on the factors moderating the relationship between the type of micro-merger and PSF performance.
This study analyzed data on three cases within University Medical Center Groningen (UMCG). Twenty-one semi-structured interviews provided the bulk of this data. The results demonstrated that Napier’s (1989) typology of mergers also applies to micro-mergers, since all three types of micro-mergers (extension, collaborative, and redesign) were identifiable.
None of these micro-merger types led to a decline in the PSF’s performance. The collaborative and redesign micro-mergers led to an increase in the PSF’s performance. Furthermore, the results indicated that merging syndrome moderates the relationship between the type of micro-merger and PSF performance. Moreover, two factors affect the severity of the merging syndrome: equivalency and feelings of unity (social identity).
Regarding future research, researchers should explore whether these results hold true for other micro-mergers. Furthermore, the conceptual framework proposed should be further explored in a quantitative matter by measuring PSF performance. Regarding managerial implications, management should be aware that governance has significant effect on the micro-merging process. Thereby, communication is key to reduce uncertainty and stress, so as to create high levels of trust.
http://scripties.umcg.eldoc.ub.rug.nl/root/anderestudie/2017/BlouwN/
Tue, 14 Mar 17 09:53:09 +0100“Risk of hemorrhage after Gamma Knife radiosurgery versus natural history for hemorrhage in brain arteriovenous malformations: a retrospective descriptive study
Background: Gamma Knife Radiosurgery (GKRS) is frequently used for the treatment of brain arteriovenous malformations (BAVM). Patients with unruptured BAVM have a risk of 2.2% per year for intracranial hemorrhage with severe morbidity and mortality[16]. Patients with ruptured BAVM have 4.5% risk for a second haemorrhage[13]. Adverse radiation effects (ARE’s) are seen post treatment with variable incidence (1.8-22.9%)[39]. The latency period post GKRS is a crucial time frame for hemorrhage and ARE’s to occur. Timely follow-up and treatment are essential during this period.
Objective: The purpose of this report was to evaluate the risk of hemorrhage post GKRS for unruptured BAVM versus the natural history, in order to conclude that treatment in unruptured BAVMs with GKRS is a good approach in preventing hemorrhages. Secondly the goal was to evaluate the risk of a second hemorrhage post GKRS in ruptured BAVM versus the rebleeding risk. The incidence of ARE’s were evaluated to analyse the safety of GKRS treatment. Lastly, to evaluate the effect of treatment, obliteration rates for hemorrhage and non-hemorrhage BAVM were analysed.
Methods: The investigation was carried through a retrospective descriptive study of patients with BAVM who underwent GKRS between 2002 and 2015 at the Gamma Knife Center of the Elisabeth-Tweesteden hospital in Tilburg, the Netherlands. Patients were included based on the inclusion criteria ( age > 18 years, angiographically established BAVM and with a minimal follow-up of ≥ 3 years). Univariate and multivariate analyses were performed. The Chi square test was used to calculate the significance level (p<0.05) of hemorrhage risk post GKRS in our study versus the bleeding risk in the natural history of BAVM. Ruptured BAVMs were compared to the rebleed risk (4.5%). Incidence rates for ARE’s were calculated. Survival analysis (Kaplan-Meier) was performed for the obliteration rates.
Results: From a total of 443 treatments, we yielded 373 BAVM treatments fulfilling the selection criteria. Out of 373 treatments, 74 were double or triple treatments and 6 patients refused further treatment. Overall we included 293 patients for further analysis of which 275 had symptomatic BAVM and 18 non-symptomatic BAVM. In the symptomatic BAVM population, the non-hemorrhage group (n =140), 2.1% (n =3) experienced hemorrhage post GKRS. In the hemorrhage group 5.9% (n=8) experienced hemorrhage post GKRS. The incidence of ARE’s is between 0.27-2%. 84 patients in the hemorrhage group and 109 patients in the non-hemorrhage group achieved full obliteration in a follow up(FU) time of 5 years.
Conclusion: We cannot conclude that in our study population the risk of hemorrhage post GKRS is significantly less, higher or the same compared to the natural history. This is due to the short follow up time (until obliteration), unequal number of patients in each group and different AVM grading system compared to other studies [16][13][39]. Also no control group could be formed due to the limited time frame for this study. What we do conclude is that patients with prior hemorrhage have a higher risk of hemorrhage post treatment; this is in line with other studies[20]. There is no difference in obliteration rate between hemorrhage and non-hemorrhage BAVM patients. GKRS could be a good and safe treatment option for symptomatic BAVM with moderate side-effects (0.27-2%) and a 60-70% complete obliteration after single treatment. For more accurate post treatment risk assessment a longer FU-time, equal distribution of patients in the comparing groups and more profound categorization of the BAVM angioarchitecture is needed.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/GovindarajanLP/
Mon, 13 Mar 17 13:22:00 +0100De relatie tussen de neonatale cerebrale oxygenatie en de vroeg neonatale neurologische uitkomst bij kinderen met ductusafhankelijke congenitale hartafwijkingen
Introductie: Ongeveer vijf tot elf per 1,000 levende pasgeborenen komen ter wereld met een congenitale hartafwijking (CHD). Dankzij verbeterde zorg bereikt tegenwoordig ongeveer 85% van deze kinderen de volwassen leeftijd. Kinderen met CHD hebben echter een hoger risico op neurologische ontwikkelingsstoornissen als gevolg van een complexe interactie tussen pre-operatieve, intra-operatieve en postoperatieve gebeurtenissen. Mogelijk ontstaat hersenschade ten gevolge van chronische foetale en vroeg neonatale hypoxie of ischemie van het brein. Een niet-invasieve en continue manier om de saturatie in het hersenweefsel te meten is door middel van near-infrared spectroscopy (NIRS). Neurologische uitkomst kan voorspeld worden door de beoordeling van general movements (GMs). Dit zijn spontane bewegingen die door het hele lichaam gemaakt worden en zeer voorspellend zijn voor latere neurologische uitkomst. In dit onderzoek wordt een correlatie gezocht tussen de kwaliteit van GMs op een leeftijd van 7 dagen en de cerebrale oxygenatie tijdens de eerste zeven dagen postnataal bij kinderen met CHD.
Methode: Kinderen met een antenataal bekende ductusafhankelijke CHD werden geïncludeerd en bij hen werd vervolgens gedurende de eerste zeven dagen de cerebrale oxygenatie door middel van NIRS gemeten. Op een leeftijd van 7 dagen werden de general movements gefilmd en vervolgens geanalyseerd.
Resultaten: Achttien kinderen in het Universitair Medisch Centrum Groningen (UMCG) werden geïncludeerd, waarvan er tien afwijkende GMs lieten zien. Er was geen relatie tussen de GMs bij zeven dagen en de cerebrale zuurstofsturatie in de eerste zeven dagen, ook niet na correctie voor de leeftijd waarop gefilmd werd.
Discussie: In een vervolgstudie zouden meer kinderen geïncludeerd moeten worden om de resultaten sterker te maken, daarnaast zouden kinderen ook bij drie maanden nog gefilmd moeten worden voor GMs, omdat dit een duidelijkere voorspeller is voor latere neurologische uitkomst.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/FeitsmaE/
Mon, 13 Mar 17 12:50:31 +0100Liver transplantation for cirrhosis secondary to non-alcoholic steatohepatitis is not performed at the expense of major postoperative morbidity
Background: Non-alcoholic steatohepatitis (NASH) is an emerging indication for liver transplantation due to the obesity pandemic. NASH frequently coexists with multiple comorbidities such as type 2 diabetes mellitus (T2DM), cardiovascular disease and the metabolic syndrome(MetS). Recent studies have shown that long-term patient and graft survival of patients transplanted for NASH cirrhosis are comparable to other indications. However, limited data exists about the short-term (procedure- related) complications after transplantation. Therefore, our aim was to investigate whether these patients are at an increased risk of short-term complications following transplantation.
Methods: This is a single centre retrospective cohort study including all adult patients (≥18 years) who underwent liver transplantation between January 2009 and December 2015 (N=224). Exclusion criteria were liver transplantation for acute hepatic failure or non-cirrhotic liver disease. Patients were censored at time of re-transplantation (n=17). Post-operative complications within 90 days were classified according to the Clavien-Dindo classification of surgical complications. NASH was defined by either: 1) histologic evidence of NASH on biopsy or explant; 2) imaging showing hepatic steatosis; 3) a phenotypic diagnosis consisting of BMI ≥ 30 kg/m2 and presence of T2DM (by either HbA1c ≥ 47 mmol/L or glucose lowering medication use) or the presence of at least 3 out of 5 diagnostic criteria for MetS as defined by the NCEP Adult Treatment Panel (ATP III). A p<0.05 was considered significant.
Results: Out of 169 eligible patients, 34 patients (20.1%) were transplanted for NASH cirrhosis. Patients with NASH cirrhosis were significantly older (59.2 vs. 54.8 years, p=0.011), more often obese (BMI≥30 kg/m2) (61.8% vs. 8.1%, p<0.001), had more T2DM (73.5% vs. 20.0%, p<0.001) and were more likely to meet criteria for MetS (83.3% vs. 37.8%, p<0.001). In univariate analysis, this group suffered from more grade I complications (p=0.016) and more grade II urogenital infections (47.1% vs. 20.0%, p=0.001). Major complications as well as 90-day graft survival in both groups was similar.
Conclusion: In patients transplanted for NASH cirrhosis postoperative major morbidity and mortality rates were comparable with patients transplanted for other indications, despite increased (minor) grade I postoperative complications.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/DouwesR/
Wed, 08 Mar 17 13:27:30 +0100Terminal cancer and suicide in older people; clinical characteristics and motives
Background: Terminally ill people represent a unique group where suicide may be considered as a rational and ethical act. Given their limited life expectancy and wish to reduce suffering, terminally ill people may exert their self-determination and autonomy by ending their life. Objectives: The aims of this study are to [i.] compare the socio-demographic and clinical variables of two groups of older people who completed suicide: those with advanced cancer and those without; and [ii] examine qualitatively whether the advanced cancer cases could be defined as rational suicide.
Methods: The New Zealand Coronial Services provided records of all suicide cases aged 65 years and over (n=225) between July 2007 and December 2012. We were able to determine whether there was an advanced cancer in 214 cases.
Findings: 23 (10.7%) older people who completed suicide were diagnosed with an advanced cancer. Bivariate analysis found that they were more likely to be male (91.3% versus 72.3%, p=0.048), married or in a defacto relationship (78.3% versus 46.1%, p=0.014); but less likely to have a diagnosis of depression (8.7% versus 46.6%, p=0.001), previous contact with psychiatric services (4.5% versus 35.0%, p=0.004) and past suicide attempt (9.1% versus 28.8%, p=0.048). Next to that the circumstances of 82.6 % of the advanced cancer patients who died by suicide were conceived as ‘understandable for uninvolved observers’.
Conclusions: With a growing elderly population and higher rates of suicide within the elderly, late-life suicide is becoming more prevalent. The diagnosis of terminal illness is higher amongst elderly. Further research is needed to delineate motives and suicide risks for terminally ill patients. More knowledge and understanding can offer the patient more targeted care and an earlier/better relieve of their mental and physical suffering.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/DouwesG/
Wed, 08 Mar 17 13:17:51 +0100Renal function more than twenty years after cisplatin-based chemotherapy fortesticular cancer
Background
The introduction of platinum-based chemotherapy for treatment of metastatic testicular cancer in the late 1970s has led to an increase in survival rates and a growing cohort of testicular cancer survivors. Consequently, attention for long-term adverse effects of treatment has increased. Nephrotoxicity is an important adverse effect of platinum-based chemotherapy. However, data on renal function more than 20 years after treatment is lacking.
Aims
1. To assess renal function and glomerular damage in very long term survivors of testicular cancer treated with cisplatin combination chemotherapy, compared with an age-matched control group who have not been treated for any type of cancer.
2. To investigate disease and treatment characteristics of testicular cancer associated with decreased renal function.
3. To investigate comorbidities and cardiovascular risk factors associated with decreased renal function.
Methods
Renal function, measured by mean creatinine clearance (CRCL) of two 24-hour urine collections, was assessed in 54 patients treated with platinum-based chemotherapy for testicular cancer between 1977 and 1996 and compared with a group of 27 healthy controls. Glomerular damage was measured by albuminuria and proteinuria and compared between the two groups. Furthermore, disease and treatment characteristics, comorbidities and cardiovascular risk factors were evaluated.
Results
Median CRCL in 54 chemotherapy-treated testicular cancer survivors was 102.8 ml/min/1.73m2 versus 125.8 ml/min/1.73m2 in healthy controls (p<0.001). 20 participants had a CRCL <90 ml/min/1.73m2, of which nineteen (95%) were treated with chemotherapy (p=0.002). No significant difference in presence of albuminuria and proteinuria was observed. Cumulative dose of cisplatin did not correlate with CRCL (spearman’s rho=0.006, p=0.967). In testicular cancer survivors, CRCL before start of chemotherapy was the only factor associated with a decreased renal function, after a median follow-up of 27 years. No differences in comorbidities and cardiovascular risk factors were observed in patients with a decreased and normal renal function.
Conclusion
Renal function in patients treated with platinum-based chemotherapy for testicular cancer more than 20 years ago is decreased compared to healthy controls. After a median follow up of 27 years, over a third of patients treated with platinum-based chemotherapy showed a decreased renal function (CRCL <90 ml/min/1.73m2). Renal function before start of chemotherapy is an important predictor for renal function in the long-term. Further research in relation to treatment related collateral damage and strategies for prevention of cisplatin-induced nephrotoxicity is needed.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/DonkerbroekJW/
Wed, 08 Mar 17 13:07:29 +0100Titration of oxygen therapy in critically ill emergency department patients: a feasibility study
Introduction- Oxygen is one of the most widely used drugs and is applied across the wide range of specialities. Liberal use of oxygen to reassure oxygen delivery has become standard treatment in resuscitation: in the ambulance, the emergency department (ED) and the intensive care unit (ICU). Today, most health care professionals do not adjust the amount of oxygen given when patients reach a saturation of 100% or a PaO2 which exceeds the normal range, resulting in hyperoxia. Because oxygen is a vital element, toxicity is not immediately obvious, but there is increasing evidence for the toxic effects of hyperoxia. Because of these potential harmful effects of hyperoxia it seems justified to aim for normoxia when giving oxygen therapy. Objective- This study aims to evaluate whether it is feasible to aim for normoxia when giving oxygen therapy to critically ill patients at the ED. Material and methods- This study was a prospective cohort study and was performed at the ED of the University Medical Center Groningen (UMCG). A protocol was developed, aiming for normoxia: PaO2 9,5-13,5 kPa or a corresponding oxygen saturation 94-98%. Hyperoxia was defined as PaO2 > 13.5 kPa or SaO2 > 98%, and hypoxia as PaO2 < 9.5 kPa or SaO2 < 94%. During a 14 week period all patients >18 years admitted to the ED that were registered for cardiology, internal medicine, emergency medicine and pulmonology requiring oxygen therapy (according to the judgement of the ambulance nurse, ED nurse or ED physician) were included. Results- During the study period the protocol was followed and normoxia was obtained in 140 of the 162 study patients (86%). Patients in which the protocol was not successful were mostly severe COPD (GOLD III/IV) patients (P<0.001) and patients with a COPD exacerbation (P= 0.03). Furthermore we found that in patients arriving with prehospital oxygen the protocol was more often not followed. Among the patients who received prehospital oxygen, patients arriving with a NRM (non-rebreather mask) were more often hyperoxic (P <0.001) on arrival at the ED compared to patients arriving with oxygen via a nasal cannula. Conclusion- This study showed that it is feasible to titrate oxygen therapy to normoxia at the ED. These study results will be used for further research assessing the feasibility of normoxia and its potential beneficial effects compared to hyper- or hypoxia in ED patients.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/DobbeA/
Wed, 08 Mar 17 12:54:03 +0100Novel insights into pure and mixed clear cell carcinomas in endometrial cancer
background
Endometrial clear cell carcinoma (CCC) and mixed endometrioid carcinoma with a clear
cell component (EEC-CC) are rare forms of endometrial carcinoma (EC). Traditionally,
these tumors are classified and treated as high grade tumors. However, just a few studies
have identified clinical outcome for patients with pure CCCs and little is known
about the overall survival of the mixed carcinomas. Also, the predictive value of pipelle
in subtyping these tumors has not yet been determined. Lastly, determining an immunoprofile
of these tumors could bring new insights in the pathogenesis of these tumors
and be of potential diagnostic aid.
methods
We selected and revised 51 pure CCCs and 28 mixed EEC-CC cases diagnosed since 1980
in the UMCG and Isala Zwolle. Clinical outcome of these patients were compared to each
other. We also selected these patients for determining the positive predictive value of
pipelle compared to the definitive diagnosis on hysterectomy. Immunohistochemical
staining for ER, PR, PTEN, p53, HNF1-β, Napsin A, AMACR, p16 and MMR, which are
common markers used for CCC and endometrioid carcinoma, were performed on all
pure CCC and both components of the mixed carcinomas to obtain an immunoprofile of
these tumors.
results
We found an overall 5-year survival rate of 64% for CCC, compared to 68% for mixed
EEC-CC, which was not statistically significant. The positive predictive value of pipelle
for detecting a pure CCC is 100%, compared to 50% for a mixed EEC-CCC.
We found the immunophenotype of ER– and PR– (71.8-95.2% resp. 87.5-92.9%),
HNF1-β+ (61.9-91.7%) to be most common in all pure CCC cases. Loss of PTEN expression,
a p53 mutation and positive Napsin A was present in about 50% of all CCC and
AMACR immunoreactivity was present in 33%. For mixed carcinomas ER, PR and HNF1-
β expression significantly differed in expression between the endometrioid and clear
cell component. The clear cell component of the mixed tumor did show a significant
lower expression for HNF1-β and Napsin A compared to a pure CCC. Microsatellite instability
for MSH2/MSH6 was also significantly higher for mixed carcinomas compared to
pure CCC.
conclusion
The outcome of mixed carcinoma is not significantly different from a pure CCC, despite
the presence of a low-grade endometrioid component. Also, pipelle is highly predictive
for detecting a pure CCC, while correctly diagnosing just half of all mixed carcinomas.
An immunoprofile of loss of ER, PR and positive HNF1-β was most common in CCC of
our study. Furthermore, the immunoprofile of the CC component in mixed EEC-CC is
intermediate between pure CCC and EEC, suggesting a common pre-existing endometrioid
lesion from which the clear cell component originates.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/DijkstraMD/
Wed, 08 Mar 17 12:33:58 +0100Non-invasieve Cardiac Output Monitoring (NICOM®) als voorspeller van de respons op volumetherapie bij septische patiënten
Background: Sepsis is a major public health problem with a high level of mortality. The initial treatment of sepsis is based on the admission of intravenous fluid which significantly decreases the sepsis-related morbidity and mortality. However, only 50% of the patients are volume responders. When fluid therapy does not increase cardiac output (CO) or stroke volume (SV) it is useless and this overuse could be harmful, resulting in an increase of complications and mortality. This shows the importance of accurate admission of intravenous fluids to enhance the treatment of septic patients and minimalize the risks of excessive – or insufficient volume therapy. A method for noninvasive continue CO measurement is NICOM®, which uses bioreactance.
Objective: The purpose of this study is to evaluate the ability of the CO measured by NICOM® in combination with several standard measured clinical parameters to predict fluid responsiveness in septic patients. The use of clinical parameters appears to be insufficiently reliable for predicting fluid responsiveness.
Methods: During a period of 14 weeks, all patients admitted to the emergency department with suspected infection will be screened. If included, the first NICOM® measurements will be recorded 10 minutes after arrival (T0). Simultaneously, several hemodynamic – and metabolic parameters are registered. This process repeats for each admission of 500 ml fluids until discharge. A response to fluid therapy is defined as an increase in SV of at least 10% after fluid admission.
Results: In total, 38 septic patients who received fluid therapy were included, of which 66% were fluid responsive after infusion of 500 ml NaCl. After infusion of 1000 ml NaCl 81% of the study population were responder. Baseline characteristics including parameters measured by NICOM® and the clinical shockscore showed no differences between responders and non-responders and were not reliable for predicting fluid responsiveness in the total study population. However, the clinical shockscore was significantly higher in responders compared to non-responders in the severe septic patients. If patients were divided into responders/non-responders after 1000 ml fluid infusion, none of the non-responders showed a response after infusion of 1500 ml NaCl (NPV=100%, 95% CI=19,7-100).
Conclusion: Although NICOM® is able to monitor fluid responsiveness, it seems difficult to predict the response based on patient characteristics on baseline. For certain patients, infusion of 500 ml fluid therapy does not seem sufficient to induce an increase in SV. For this reason, the classification into responders and non-responders should be made after infusion of 1000 ml fluid therapy. If patients have not responded to fluid therapy at that time, the continuation of fluid infusion seems useless. The use of NICOM® could be beneficial in guiding fluid therapy, nevertheless further research is required to confirm this.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/DijkstraJ/
Wed, 08 Mar 17 12:16:46 +0100The effect of Deep Brain Stimulation on Corticomuscular Coherence in Parkinson's Disease
Background: In advanced Parkinson’s disease (PD), deep brain stimulation (DBS) is considered as an ultimate treatment; however inefficacy and side-effects remain a challenge. A reliable, non-invasive neurophysiological biomarker could be valuable enabling the application of DBS in a highly selective way. Corticomuscular coherence (CMC) could be used as a potential biomarker. CMC is seen as a representation of the co-operation between brain areas and muscles in motor tasks and is present in PD symptoms of tremor (tremor frequency range) and akinesia-rigidity (beta range).
Aim: To test CMC, measured by electroencephalography (cortex) and electromyography (muscles), as a potential biomarker for improvement in tremor and akinesia-rigidity after DBS.
Methods: In this single center prospective cohort pilot study, five tremor-dominant and five akinetic-rigid PD DBS candidates of the University Medical Centre Groningen (UMCG) were included. In the akinetic-rigid PD group, beta CMC was measured during a flexion, pinching and resting task; symptoms were assessed by the MDS-UPDRS III upper body akinetic-rigid items. In the tremor-dominant PD group, tremor CMC was retrieved during a maximal tremor task; symptoms by use of a clinical tremor score and accelerometer. Change in CMC after DBS was tested and correlations were performed between CMC and symptom severity. Thereafter, correlations between change in CMC and improvement in symptoms; and pre-DBS CMC and improvement in symptoms were made.
Results: Tremor CMC decreased significantly after DBS (p=0.01) and significantly correlated with tremor severity (p<0.01). No relation between the decrease in tremor CMC and tremor reduction; and between pre-DBS CMC and tremor reduction was found. No significant increase in akinetic-rigid PD total beta CMC was detected after DBS and no relation with severity and improvement in akinesia-rigidity was seen. However, high beta CMC during flexion did correlate with severity (rs =-0.45; p<0.05), and improvement in akinesia-rigidity correlated with the percentage increase in high beta CMC and high beta CMC pre-DBS (rs =0.75, p=0.01; rs =-0.71, p=0.02).
Conclusion: Correlations between high beta CMC with symptom severity and clinical effect during flexion in the akinetic-rigid PD group were found; in the tremor-dominant PD group, CMC did decrease significantly and was associated with symptom severity. However, the beta CMC was insignificantly increased after DBS in the akinetic-rigid PD group and there were lack of correlations between tremor CMC and clinical effect in the tremor-dominant PD group. Further, due to the small sample size in this pilot study, utility of CMC as a potential biomarker cannot be recommended yet and further research on a larger scale is strongly advised.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/DijksJG/
Tue, 07 Mar 17 10:36:53 +0100Imaging Characteristics and Recurrence Patterns of the Subventricular Zone in Glioblastoma
Glioblastomas (GBMs) are the commonest and most malignant primary brain tumour. It is suggested that GBMs can arise from neural stem cells within the subventricular zone (SVZ). However, evidence demonstrating these cancer stem cells in GBM is lacking. This study aimed to identify the imaging characteristics of the SVZ and its relation to recurrent disease in patients with GBM by using multimodal imaging.
We included 99 primary GBM patients who underwent preoperative multimodal imaging. Follow-up data was available for 33 patients. Initial and recurrent tumours were classified into SVZ contacting and non-contacting GBMs. Diffusion and perfusion parameters were calculated in SVZ related and SVZ non-related regions.
Diffusion imaging showed signs of tumour infiltration in the SVZ with high FLAIR signal. Furthermore we found that over half of the patients with an initial SVZ non-contacting tumour recurred within the SVZ. These patients showed increased diffusion parameters in the SVZ compared to locally recurrent tumours on preoperative imaging.
Our diffusion parameters were able to show the presence of tumour cells within the SVZ, which supports the presence of a SVZ component in GBM. Preoperative evaluation of the SVZ with diffusion MRI was able to detect signs of tumour infiltration and can predict patterns of GBM recurrence within the SVZ.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/DijkenBRJvan/
Tue, 07 Mar 17 10:12:05 +0100Neonatal sepsis incidence in preterm infants treated with standard care in an open bay in a level 2 Neonatal ward,2009-2012.
Background and objective Neonatal sepsis is a severe disease in preterm infants that can
result in significant morbidity in this vulnerable patient group. Our aim was to identify and
assess the risk factors and incidence of neonatal sepsis in two different groups of preterm
infants (very preterm-and moderate to late preterm infants) in a level 2 neonatal ward.
Methods We conducted a retrospective cohort study in preterm infants with a gestational age
(GA) of <36weeks transferred to or born in our centre from 2009 to 2012. Sepsis was defined
as a positive blood culture and clinical symptoms, with early -and late onset sepsis defined as
onset of symptoms before 72 hours and after 72 hours of life, respectively. Univariate and
multivariate logistic analyses were performed.
Results We included 163 very preterm infants (GA<32weeks) and 434 moderate-to late
preterm infants (GA 32-36weeks). Neonatal sepsis was found in 6% (36/597) of preterm
infants. There was a significant association between the type of group a neonate belonged to
(according to GA) and whether or not sepsis was diagnosed (p < 0.002). The odds of sepsis
for neonates were 2.7 times higher if they were born with a GA <32 weeks (group A) than if
they were born with a GA 32- 36 weeks (group B). Early-onset sepsis (EOS) with group B
streptococcus occurred in one late preterm infant (0.7%) of 146 suspected episodes. Lateonset
sepsis (LOS) occurred in 35 preterm infants of a total of 90 suspected episodes (39%).
Coagulase-negative staphylococci was the most frequently pathogen isolated in LOS. Total
parenteral nutrition administration, vaginal spontaneous birth and gestational age were
significantly associated with LOS.
Conclusion This study shows a very low prevalence of EOS and LOS in both very preterm
and moderate preterm infants. Vaginal spontaneous birth was found to be a significant
protective factor for LOS. TPN administration (by central venous catheter, peripheral inserted
catheter), vaginal spontaneous birth and lower GA were found to be significant risk factors
for development of LOS.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/DalenRC/
Tue, 07 Mar 17 08:51:18 +0100Local influence of rituximab and abatacept treatment on follicular helper T-lymphocytes in salivary glands of patients with primary Sjögren’s syndrome
The aim of this project was to investigate whether follicular helper T cells are present in the major salivary glands of primary Sjögren’s syndrome patients and to determine the effect of treatment with rituximab or abatacept on these cells. Furthermore, we analyzed local levels of IL21, a signature cytokine produced by Tfh-cells, before and after treatment. Tfh-cells defined by their expression of ICOS and CXCR5 were found in some, but not all patients analyzed. Also high numbers of IL21-positive cells were found in the parotid glands of all patients, and a decrease was seen in some patients after treatment with both rituximab and abatacept. Decreased expression of IL21 and CXCL13 was also seen at the mRNA level, suggesting a possible reduction in Tfh-cell activity and attraction of CXCR5+ cells into the salivary gland. Because of the small number of patients analyzed in this study, no statistically significant changes were yet detected. However, the results described here do suggest a possible local effect on Tfh-cells and other IL21-producing cells of both rituximab and abatacept in primary Sjögren’s syndrome. The presence of Tfh-cells and the high number of IL21-positive cells in the parotid glands also suggests that Tfh-cells are involved in the inflammatory process seen in pSS.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/BroekmanHLF/
Tue, 07 Mar 17 08:34:32 +0100The Role of TLR4 / uPAR interaction in microvascular inflammation found in Diabetes Mellitus
Introduction Diabetes Mellitus is a systemic disease having many adverse long-term effects on multiple organs. The incidence of both Types of Diabetes is vastly rising, affecting patients particularly in the Western World.
Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and kidney failure worldwide, being the strongest mortality predictor in patients with diabetes. Recent data revealed that Toll-like receptor 4 (TLR4)-mediated inflammation is associated with initiation and progression of DN. We hypothesized that urokinase-type plasminogen activator receptor (uPAR) might serve as a co-receptor to TLR4 in diabetes-associated inflammation.
Methods Human Microvascular Endothelial Cells (HMEC-1) were stimulated with low and high concentration of glucose to simulate diabetes. Inflammatory markers were measured via PCR and ELISA. TLR4 and uPAR expression was measured via Western blot. The interaction of the two receptors was quantified by co-immunoprecipitation and immunocytochemistry. uPAR expression was downregulated using lentiviral cell infection and glucose-dependent signaling pathways were analyzed by Western blotting.
Results Inflammatory cytokines were up-regulated in HMEC-1stimulated with high glucose. TLR4 and uPAR expression was elevated when HMEC-1 were set under diabetic conditions. TLR4/uPAR interaction could be proven in glucose induced diabetic HMEC-1. Lentiviral downregulation of uPAR proved that uPAR has a functional involvement in cellular response to high glucose in endothelial cells which is probably linked to TLR4 signaling.
Discussion/Conclusion Data suggests that TLR4/uPAR interaction plays an important role in diabetes-associated inflammation. This interaction needs to be verified and established further by in vitro studies in primary cells as well as on an in vivo model in mice. TLR4/uPAR interaction could be blocked by means of peptide inhibitors, thus having a great therapeutic impact in Diabetes associated DN.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/BrockktterLM/
Mon, 06 Mar 17 11:23:55 +0100COMPARISON OF INVASIVELY AND NONINVASIVELY MEASURED RIGHT VENTRICULAR-VASCULAR COUPLING RATIO IN PEDIATRIC PULMONARY ARTERIAL HYPERTENSION: A MULTI-CENTER STUDY
Introduction: In pediatric pulmonary arterial hypertension (PAH), RV failure is the main cause of death. Right ventricular-vascular coupling ratio (VVCR) is gaining interest as it encloses both contractility and afterload. Conventional determination of VVCR by catheterization (VVCRs) is invasive and frequently requires anesthesia. Therefore, the goal of this study was to compare the usefulness of noninvasively determined VVCR by cardiac magnetic resonance (CMR) (VVCRm) to VVCRs in pediatric PAH.
Hypothesis: We assessed two hypotheses: 1) VVCRm is a good estimate of VVCRs; and 2) both serve as good measures of disease severity and outcome.
Methods: Retrospectively, PAH patients who had catheterization and CMR within 90 days were included from two specialized PH centers. VVCR was defined as the end-systolic elastance/effective arterial elastance ratio. VVCRm as stroke volume/end-systolic volume ratio and VVCRs by single-beat method were compared using regression analysis and Bland-Altman plots. Both were correlated to disease severity (PVRi, mRAP, CI) and adverse outcome (death, lung transplantation, atrial septostomy and intravenous medication). The area under the receiver operating characteristic curve (AU-ROC), Kaplan-Meier curves and hazard ratios (HR) from Cox regression determined their value in predicting adverse outcome.
Results: In the 31 patients included (17 from CHC and 14 from UMCG), median age was 14 years (0.3 – 23) and median PVRi was 7.6 WU × m2 (2.1 – 32). VVCRm and VVCRs were strongly correlated (r = 0.78, p < 0.001) with a mean difference of 0.2 and 95% of the differences between -0.3 and 0.7. Both had comparable significant correlations with disease severity and adverse outcome. Also, both VVCRm and VVCRs were shown to be of good prognostic value with AU-ROCs of respectively 0.84 and 0.90 and HRs (95%-CI) of 0.82 (0.70 – 0.96) and 0.69 (0.53 – 0.90).
Conclusion: In line with previous research, the results of this study indicate that VVCRm and VVCRs are comparable in pediatric PAH and are both good predictors of outcome. The characteristic disease progression is clearly seen in VVCRm, but its clinical use has to be defined by further research.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/BreemanK/
Mon, 06 Mar 17 10:02:10 +0100Kanker en zwangerschap: verband tussen antenatale blootstelling aan oncologische behandeling en foetale groei. :Een retrospectief cohortonderzoek op basis van de International Network on Cancer Infertility and Pregnancy (INCIP) database.
Introductie: Het ‘International Network on Cancer, Infertility and Pregnancy’ (INCIP) publiceerde recentelijk de onderzoeksresultaten van de lange termijn gevolgen voor het kind van oncologische behandeling gedurende de zwangerschap.1 Op het vlak van algehele gezondheid, cognitief vermogen en cardiale ontwikkeling werd geen verschil gezien met de algemene populatie.1,2 Wat bij zwangeren met kanker echter opviel was dat er relatief meer small for gestational age (SGA) kinderen geboren werden (gedefinieerd als geboortegewicht <p10 op basis van de aangepaste groeigrafieken).3,4
Onderzoeksdoel: Nakijken van het effect van antenatale maternale kankerdiagnose en het type en tijdstip van oncologische behandeling op het voorkomen van SGA.
Methode: Een retrospectief cohortonderzoek werd uitgevoerd op basis van gegevens uit de INCIP database, een internationale database waarin zowel oncologische als obstetrische gegevens worden verzameld van vrouwen met een kankerdiagnose tijdens de zwangerschap. Alleen éénling zwangerschappen waarbij zwangerschapsduur bij partus en geboortegewicht gekend was, werden geïncludeerd. Het geboortegewicht werd uitgedrukt in percentielen op basis van aangepaste groeicurves. Parameters die in rekening gebracht werden zijn zwangerschapsduur bij geboorte, geslacht, lengte en gewicht van de moeder, pariteit en ras. Middels multivariabele logistische regressie zijn de individuele effecten van de parameters type behandeling, tijdstip start behandeling en type maligniteit vergeleken.
Resultaten: 614 zwangere patiënten werden geanalyseerd met bijbehorende nakomeling. De gemiddelde maternale leeftijd was 19 tot 48 jaar. Het gemiddelde geboortegewicht bedroeg 2755.7 ± 727.3 gram. Bij 136 (22.14%) nakomelingen lag het geboortegewicht onder het 10e percentiel, dit aantal is significant verhoogd in vergelijking met de algemene populatie (chi-kwadraattoets, P=<0.0001). Van de verschillende tumortypes werd SGA het meest frequent vastgesteld bij vrouwen met lymfomen (28,7%). Van het aantal patiënten met oncologische behandeling tijdens de zwangerschap (n=422) kreeg het merendeel een chemotherapeutisch gebaseerde behandeling (60,6%). Chemotherapieblootstelling was significant gerelateerd aan SGA (OR 1.69, P=0.01). Van de verschillende chemotherapeutica was blootstelling aan taxanen het sterkst geassocieerd met SGA (OR 4.88, P=0.0001). Een verband tussen het aantal toegediende chemotherapeutische cycli of moment van toediening gedurende de zwangerschap en SGA is niet waargenomen.
Conclusie: Dit retrospectief onderzoek toont aan dat er significant meer nakomelingen met SGA worden gezien bij zwangere vrouwen met een oncologische ziekte ten opzichte van de algemene populatie. Rekening houdend met de ongelijkwaardige aantallen in de behandelingsgroepen wordt met enige bedachtzaamheid geconcludeerd dat er significant meer nakomelingen met SGA geboren worden indien de zwangere behandeld wordt met (taxanen gebaseerde) chemotherapie. Gebruik van chemotherapie gedurende de zwangerschap en placentaire dysfunctie benodigd daarom verdere analyse.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/BouwmanAMG/
Tue, 28 Feb 17 11:15:32 +0100The CHOPIN study : A multicenter study on Cerebellar Hemorrhage and Outcome in Preterm Infants
Objective: To investigate the association between size, number and location of cerebellar hemorrhage (CBH) and neurodevelopmental outcome in very preterm infants, diagnosed with either isolated CBH or combined CBH and supratentorial brain lesions. Secondly, the aim is to investigate associations between perinatal, postnatal and maternal factors and CBH.
Methods: A cohort of preterm infants (≤ 34 weeks) born between 2006 and April 2016, and admitted to one of the three participating Dutch NICUs, was generated. Data (perinatal factors, neuro-imaging and follow-up at 2 years) were retrospectively collected. MRI and/or cranial ultrasound scans were reassessed to determine the exact size, number and location of CBH and the presence of supratentorial injury. Infants were divided between two groups: punctate CBH (≤ 4 mm) or major CBH (> 4 mm). The composite outcome score for neurodevelopmental outcome was defined by the result of the Bayley Scale of infant Developmental (BSID) test and the neurological examination.
Results: Data of 111 preterm infants were analyzed. Of 56 infants the composite outcome score could be obtained. Seven out of 14 infants (50%) with major CBH and 17 out of 42 (40%) with punctate CBH had an abnormal composite outcome score. Laterality of CBH and vermian lesions were not significant associated with an abnormal composite outcome score. HFO ventilation ventilation and supratentorial injury were independent risk factors for an abnormal composite outcome score. Independent risk factors for the occurrence of major CBH were gestational age (correlated with birth weight), forceps or ventouse delivery, severe thrombocytopenia (with a platelet count < 50) and maternal age.
Conclusion: Our results show that major CBH is associated with an unfavorable outcome when compared to punctate CBH. No evident association between the size and location of CBH and outcome was found. However, the study population was too small to draw firm conclusions.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/BoswinkelV/
Tue, 28 Feb 17 10:58:35 +0100De toegevoegde waarde de nekplooi meting in vergelijking met niet invasieve prenatale screening
Background and Objectives The Dutch Ministry of Health, Welfare and Sport is expected to take a decision on short term on the provision of Non-Invasive Prenatal Testing (NIPT) in the 10th week for all pregnancies. Herewith the current combined testing in the first trimester, with the Nuchal Translucency (NT) measurement as part, may completely disappear. However, it is confirmed that the predictive value of increased NT goes further than only diagnosing Trisomy 13, 18 and 21. The aim of this study is to identify on a national level what exactly the added value of NT measurement is, by discovering how many and which abnormalities can be detected by an NT measurement. That way, it can be mapped out which consequences the disappearance of combined testing will have; in other words which abnormalities might be delayed or not at all be diagnosed. Methods From the databases of four academic hospitals 16003 pregnancies were selected, whereby combined testing was performed in the first trimester of the pregnancy during the period 01-01-2010 up to and including 31-12-2015. Pre- and postnatal information, with emphasis on results of karyotyping, advanced ultrasound examination, post-mortem results and consultations by the clinical geneticist, was retrospectively collected and analyzed of all pregnancies with an increased NT (>95th percentile). Results 1390 fetuses (8.7%) had an increased NT; nearly half of them had an abnormality. 535 were diagnosed with Trisomy 13,18 or 21 and thus were potentially detectable by NIPT. 271 had a structural, genetic or rare chromosomal abnormality which was not detectable by NIPT. If NIPT will replace combined testing as screening method in the first trimester of the pregnancy, the consequence will be that the opportunity of early warning and diagnosing will be missed for these abnormalities. Conclusion Ideally both (screening)tests should be used in parallel. That way Trisomy 13, 18 and 21 can be diagnosed with high sensitivity and specificity and invasive procedures are less needed. On the other hand, using the NT measurement, adequate counseling and early diagnosis of severe abnormities can be accomplished, such preventing unpleasant surprises at the 20th week of pregnancy. Also in case of severe anomalies an earlier pregnancy termination is less traumatic for the mother. In addition, the missed cases of mainly Trisomy 13 and 18, where NIPT is less accurate, and where the NT is often thickened, yet can be diagnosed early.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/BosschieterPFN/
Mon, 27 Feb 17 12:51:07 +0100Impact of Vedolizumab and anti-TNF biologics on Sleep Qualityand Mood in Inflammatory Bowel Diseases: A Prospective Study
Introduction
Poor sleep, depression, and anxiety are common in patients with inflammatory bowel diseases (IBD) and associated with increased risk of relapse and poor outcomes. The effectiveness of therapies in improving such psychosocial outcomes is unclear but is an important question to examine with increasing selectivity of therapeutic agents.
Methods
This prospective cohort enrolled patients with moderate-to-severe CD or UC starting biologic therapy with vedolizumab or anti-tumor necrosis factor α agents (anti-TNF). Sleep quality, depression and anxiety were measured using validated short form NIH PROMIS questionnaires assessing sleep and mood quality over the past 7 days. Disease activity was assessed using validated indices. Improvement in sleep and mood scores from baseline was assessed and regression models were used to identify determinants of sleep quality.
Results
Our study included160 patients with IBD (49 anti-TNF, 111 Vedolizumab) among whom half were women and the mean age was 40.2 years. In the combined cohort, we observed a statistically significant and meaningful decrease in mean scores from baseline (52.8) by week 6 (49.8, p=0.002). Among vedolizumab users, sleep T-score improved from baseline (53.6) by week 6 (50.7) and persisted through week 54 (46.5, p=0.009). Parallel reductions in depression and anxiety were also noted (p < 0.05 by week 6). We observed no difference in improvement in sleep, depression, and anxiety between vedolizumab and anti-TNF use at week 6.
Conclusions
Both vedolizumab and anti-TNF biologic therapy was associated with improvement in sleep and mood quality in IBD.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/BorrenNZ/
Mon, 27 Feb 17 12:19:08 +0100The influence of BMI and smoking at disease onset on long-term joint damage measured with the RAAD score in patients with rheumatoid arthritis
Introduction: after the development of new effective medication and the introduction of “treat-to-target” strategies directed at obtaining remission, the prognosis of RA greatly improved. Remarkably, obesity is named as a predictor of less radiographic progression. The literature is not clear about the relation between body mass index (BMI) and long-term joint damage. Little evidence about the long-term effect of smoking on joint damage is available. Time consuming radiographic scoring methods, such as the Sharp van der Heijde (SHS) and Larsen score, are frequently used in clinical research to evaluate joint damage of hands and feet. In order to have an easy applicable instrument to measure joint damage, Zijlstra et al. developed the RAAD score in 2002. A high correlation between the RAAD score and the SHS has been found. The present study investigated whether BMI and smoking at the moment of diagnosis are related with irreversible joint damage at long-term, measured with the RAAD score.
Patients and methods: the research population consists of all patients who received treatment for RA in the ZGT from January 1996 until December 2015. From this population patients with a RAAD score, determined between 2014 and April the first of 2016, and a disease duration of at least five years at the moment of the RAAD score were included. Baseline data were collected through retrospective record research and through verifying information during an outpatient visit. Smoking at disease onset was categorized in three groups: current smoker, former smoker, non smoker. Mann Whitney U tests, Spearman’s correlations, Kruskal-Wallis tests and multivariate regression analysis were performed.
Results: baseline characteristics study population (n=521): 67.8% woman, mean (SD) age in years 49.0 (13.7), mean (SD) BMI in kg/m2 25.7 (3.9), 79.5% RF positive, 72.6% anti-CCP positive, 36.8% non smoker, 28.4% former smoker, 34.8% smoker. Median [IQR] RAAD score was 2.0 [0-6.0]. A significant, weak correlation between BMI and the RAAD score (correlation coefficient -0.14, p=0.003) was found. No significant difference in RAAD score was found between patients with different smoking status. Obviously, the RAAD score was correlated with disease duration, irreversible damage can only increase. Disease duration was correlated with BMI. There was an increasing trend in BMI at disease during the decades. When corrected for this trend, through adjusting for disease duration, no significant correlation was found between BMI and the RAAD score.
Conclusion: BMI and smoking status at the moment of diagnosis of RA are not related with irreversible joint damage at long-term as measured with the RAAD score, when adjusted for disease duration. For the trend in BMI throughout the decades was corrected with disease duration.
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/BoesES/
Wed, 22 Feb 17 10:31:27 +0100